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1.
Orthop J Sports Med ; 11(2): 23259671221149373, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36860773

RESUMO

Background: The outbreak of the 2019 novel coronavirus disease (COVID-19) led to an enforced quarantine period and limited training and match activities for athletes. Purpose: To report the influence of the COVID-19 pandemic on the occurrence of injury in Japanese male professional soccer players. Study Design: Descriptive epidemiology study. Methods: In total, 21 clubs in the 2019 season and 28 clubs in the 2020 season from the Japan Professional Football League were prospectively followed, and 16 clubs in 2019 and 24 clubs in 2020 were analyzed in this study. Individual training, match exposure, and time-loss injuries were recorded using an electronic data capture system. The influence of COVID-19-related suspension during the 2020 season was retrospectively investigated via comparisons with the 2019 season. Results: Total activity time included 114,001 hours in training and 16,339 hours in matches in 2019 and 170,798 hours in training and 25,411 hours in matches in 2020. The mean training interruption period caused by COVID-19 in 2020 was 39.9 days (range, 3-65 days), and the mean game-interruption period was 70.1 days (range, 58-79 days). The total number of injuries was 1495 in 2019 and 1701 in 2020. The overall injury incidence per 1000 hours of exposure was 5.7 in 2019 and 5.8 in 2020. The overall injury burden per 1000 hours of exposure was 155.5 days in 2019 and 130.2 days in 2020. The muscle injury incidence was highest in May 2020, immediately after the suspension period. Conclusion: The overall injury incidence did not differ between 2019 and 2020. However, muscle injury incidence notably increased in the 2 months after the COVID-19 pandemic suspension period.

2.
Eur J Orthop Surg Traumatol ; 33(2): 361-366, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34988722

RESUMO

BACKGROUND: Return to sports is one of the important reasons why athletes with an anterior cruciate ligament (ACL) injury undergo surgery. There are few reports on return to sports among adult amateur athletes (individuals older than the college age who participate in competitive sports). This study aimed to investigate the return of adult amateur athletes to competitive sports 1 year after ACL reconstruction and to identify the indicators for return to competitive sports. METHODS: Between January 2015 and December 2017, adult amateur athletes who underwent primary ACL reconstruction were retrospectively investigated. The rate of return to competitive sports 1 year after surgery was evaluated. The patients were categorized into two groups: return to sports group (R group) and non-return to sports group (N group). Pre- and postoperative range of motion, pivot-shift test, anteroposterior laxity, quadriceps strength, Lysholm score, and the International Knee Documentation Committee score were compared between the groups. RESULTS: This study included 78 patients (48 men, 30 women; age range, 22-53 years). Five months after ACL reconstruction, quadriceps strength was significantly lower in the N group than in the R group, denoting muscle weakness in the N group at that time. No significant differences were found in the other items between the groups preoperatively and 1 year after surgery. CONCLUSION: In this study, the rate of return to competitive sports of adult amateur athletes 1 year after ACL reconstruction was 76.9%. Quadriceps strength may be an early indicator of return to competitive sports 1 year after reconstruction.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Masculino , Humanos , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Estudos Retrospectivos , Recuperação de Função Fisiológica , Articulação do Joelho/cirurgia , Atletas , Lesões do Ligamento Cruzado Anterior/cirurgia
3.
J Foot Ankle Surg ; 61(4): 807-811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34973864

RESUMO

Surgery with autologous bone grafting for proximal fifth metatarsal diaphyseal stress fracture has a potential to decrease nonunion, but it is not performed widely as the primary surgery because of donor-site morbidity. We have devised and performed a less invasive surgical procedure with autologous bone grafting and aimed to investigate the clinical and radiologic outcomes of this procedure. The data for 73 patients who underwent primary intramedullary screw fixation with autologous bone grafting from the fifth metatarsal base for proximal fifth metatarsal diaphyseal stress fractures were investigated retrospectively. The clinical and radiologic outcomes were evaluated. The mean time to bone union, starting running, and return to play was 11.8, 6.3, and 13.4 weeks, respectively. Bone union was achieved in 76 of the 78 cases. Intramedullary screw fixation with autologous bone grafting from the fifth metatarsal base showed good outcomes. It may be a useful surgical option for patients with proximal fifth metatarsal diaphyseal stress fractures.


Assuntos
Doenças Ósseas , Doenças das Cartilagens , Fraturas Ósseas , Fraturas de Estresse , Ossos do Metatarso , Transplante Ósseo/métodos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/cirurgia , Humanos , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Estudos Retrospectivos
4.
J Foot Ankle Surg ; 61(2): 355-362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34656416

RESUMO

Mini-incision surgical procedures in our institution have been developed by decreasing the total skin incision length from the original mini half-Bunnell tendon repair technique. We hypothesized that the mini-incision, or minimum invasive Achilles tendon repair technique, would promote the tendon healing process leading to better outcomes and a reduced complication rate compared to the conventional open repair. The study sought to determine the more optimal method by comparing 44 mini-incision sutures to the 99 sutures in the original open Achilles tendon repairs. The mean skin incision length of the mini-incision surgery was 2.9 (range 2.5-3.0) cm and the original repair was 4.2 (range 3.5-7.0) cm. The mean surgery time was 60.0 minutes in the mini-incision repair and 68.1 minutes in the original one (p = .0003). The mean achievement time of bilateral heel-rise, starting jogging, single-legged heel-rise movement and the time to return-to-play was not significantly different between the 2 groups. Achilles Tendon Rupture Score was not significantly different from 3 to 9 months after surgery. Re-injury rate was 1/44 (2.3%) in mini-incision and 4/99 (4.0%) in conventional open repair (p = .36). No patients in either group developed any postoperative infections nor deep vein thrombosis complications. Although the mini-incision half-mini-Bunnell suture was showed equivalent clinical results to the original open repair, the technique is recommended in terms of curtailment of the surgery time without increase of complication ratio.


Assuntos
Tendão do Calcâneo , Procedimentos Ortopédicos , Traumatismos dos Tendões , Tendão do Calcâneo/lesões , Tendão do Calcâneo/cirurgia , Humanos , Procedimentos Ortopédicos/métodos , Ruptura/cirurgia , Técnicas de Sutura , Traumatismos dos Tendões/cirurgia , Resultado do Tratamento
5.
J Exp Orthop ; 8(1): 86, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34617148

RESUMO

PURPOSE: The anterior cruciate ligament (ACL) reconstruction via a contralateral bone-tendon-bone (C-BTB) autograft was introduced to encourage early return to sports. The purpose of this study is to evaluate whether primary contralateral BTB ACL reconstruction can be adapted for early return-to-sports modification by investigating the chronological changes of muscle strength after surgery. METHODS: Fifteen patients who had underwent C-BTB ACL reconstruction were compared with a matched group of 15 patients of ipsilateral BTB (I-BTB) ACL reconstruction. The clinical outcomes of the time of return-to-sports, Tegner activity scale and the rate of second ACL injuries, the tibial anterior translation measurement, and knee extension and flexion muscle strength were assessed. RESULTS: Within 12 months after surgery, 14 of 15 patients from both groups returned to preinjury sports. The median time to return to sports after surgery was 6.5 months in the C-BTB group and 8.0 months in the I-BTB group (p = 0.021). No significant difference was noted with regard to the Tegner activity scale, reinjury rate or mean instrumental anterior tibial translation. The quadriceps muscle strength in the ACL-reconstructed knee compared with the opposite knee in both groups at 5 months after surgery was 120.6% in the C-BTB group and 70.0% in the I-BTB group (p < 0.001). However, the quadriceps muscle strength of the non-reconstructed limb, which instructed the graft harvested knee in the C-BTB and the intact knee in the I-BTB group, compared with that of the preoperative uninjured limb, was 74.5% in the C-BTB group and 118.7% in the I-BTB group (p = 0.0021) 5 months after surgery. Moreover, the quadriceps muscle strength of the reconstructed knee compared with the preoperative normal limb was 88.8% and 81.5% in the C-BTB and I-BTB groups, respectively (p = 0.38). CONCLUSIONS: ACL reconstruction via the C-BTB autograft indicated better quadriceps muscle strength from early stage after surgery compared with I-BTB ACL reconstruction. However, the ostensible rapid symmetrical muscle strength recovery was attributed to strength deficits compared to the preoperative condition at the donor site limb and ACL-reconstructed limb. LEVEL OF EVIDENCE: Level: Level: 4.

6.
BMC Musculoskelet Disord ; 22(1): 725, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425817

RESUMO

BACKGROUND: Intramedullary screw fixation is considered the standard treatment for proximal fifth metatarsal stress fractures. Low-intensity pulsed ultrasound (LIPUS) is a well-known bone-healing enhancement device. However, to the best of our knowledge, no clinical study has focused on the effect of LIPUS for postoperative bone union in proximal fifth metatarsal stress fractures. This study aimed to investigate the effect of LIPUS treatment after intramedullary screw fixation for proximal fifth metatarsal stress fractures. METHODS: Between January 2015 and March 2020, patients who underwent intramedullary screw fixation for proximal fifth metatarsal stress fractures were investigated retrospectively. All patients underwent intramedullary screw fixation using a headless compression screw with autologous bone grafts from the base of the fifth metatarsal. The time to restart running and return to sports, as well as that for radiographic bone union, were compared between groups with or without LIPUS treatment. LIPUS treatment was initiated within 3 weeks of surgery in all cases. RESULTS: Of the 101 ft analyzed, 57 ft were assigned to the LIPUS treatment group, and 44 ft were assigned to the non-LIPUS treatment group. The mean time to restart running and return to sports was 6.8 and 13.7 weeks in the LIPUS treatment group and was 6.2 and 13.2 weeks in the non-LIPUS treatment group, respectively. There were no significant differences in these parameters between groups. In addition, the mean time to radiographic bone union was not significantly different between the LIPUS treatment group (11.9 weeks) and the non-LIPUS treatment group (12.0 weeks). The rate of postoperative nonunion in the LIPUS treatment group was 0% (0/57), while that in the non-LIPUS treatment group was 4.5% (2/44). However, this difference was not statistically significant. CONCLUSIONS: There were no statistically significant differences regarding the time to start running, return to sports, and radiographic bone union in patients with or without LIPUS treatment after intramedullary screw fixation for proximal fifth metatarsal stress fractures. Therefore, we cannot recommend the routine use of LIPUS to shorten the time to bone union after intramedullary screw fixation for proximal fifth metatarsal stress fractures.


Assuntos
Fraturas de Estresse , Ossos do Metatarso , Parafusos Ósseos , Fixação Interna de Fraturas , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/cirurgia , Humanos , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Estudos Retrospectivos , Ondas Ultrassônicas
7.
J Foot Ankle Surg ; 60(6): 1198-1203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34134918

RESUMO

The purpose of this study was to clarify the morphology of acute Achilles tendon rupture (ATR) according to intraoperative evaluation. The morphology of 220 cases was evaluated retrospectively from intraoperative findings from June 2014 to December 2015. We noted 3 characteristics of rupture. First, we divided the ruptures into complete or partial type. Second, according to the level of rupture, we classified them into muscle-tendon junctional type, mid-substantial type, or calcaneal insertional avulsion type. Lastly, on the basis of the pattern of rupture, we divided them into transverse pattern, double-layer pattern, or Z-shaped pattern. All ruptured tendons were repaired with surgical procedures on the basis of the classification of rupture type or pattern. Of the total of 220 cases, 217 were complete ruptures (98.7%) and 3 partial ruptures (1.3%). Regarding the level of rupture, 5 cases were of the muscle-tendon junctional type (2.3%), 209 cases of the mid-substantial type (95%), and 6 cases of the calcaneal insertional avulsion type (2.7%). In terms of the pattern of rupture, there were 198 cases of the transverse pattern (90%), 10 cases of the double-layer pattern (4.5%), and 12 cases of the Z-shaped pattern (5.5%). There was significant gender difference only in the mid-substantial type. Although the morphology of a typical acute ATR was complete, of mid-substance type, and with transverse pattern, other types of ATR were recognized from the intraoperative investigation.


Assuntos
Tendão do Calcâneo , Calcâneo , Traumatismos dos Tendões , Tendão do Calcâneo/cirurgia , Humanos , Estudos Retrospectivos , Ruptura/cirurgia , Traumatismos dos Tendões/cirurgia
8.
Arthrosc Sports Med Rehabil ; 3(1): e47-e55, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33615247

RESUMO

PURPOSE: To assess the clinical outcomes comparing rectangular bone-tendon-bone (BTB) grafts and double-bundle hamstring tendon (HM) grafts used for anatomic anterior cruciate ligament (ACL) reconstruction in young female athletes. METHODS: From January 2014 to November 2017, young female athletes 20 years or younger who underwent primary ACL reconstructions by a single surgeon were identified. Patients with concomitant injuries, not being a regular sports participant, the existence of contralateral ACL reconstruction, and who did not have a minimum of 1-year follow-up were excluded. We searched the rate and time for return-to-play, clinical outcomes including chronological instrumental side-to-side tibial translation difference, and muscle strength. Second ACL injury rates between the 2 groups during follow-up period were evaluated. RESULTS: Twenty-seven BTB ACL reconstructions and 29 HM ACL reconstructions were performed. The mean follow-up periods were 35.2 months in the BTB group and 33.8 months in the HM group. The BTB group showed better knee stability in mean side-to-side translational difference via arthrometric testing of 0.6 mm in the BTB versus 1.7 mm in the HM group at 5 months (P = .01) and 1.1 mm and 2.0 mm at 12 months, respectively (P = .02). There was no significant side-by-side difference in quadriceps muscle strength ratio, but the hamstring muscle strength was significantly better in the BTB group. The graft reinjury rate in the BTB group and the HM group was 0% (0/27) and 10.3% (3/29) (P = .09), respectively. In contrast, contralateral ACL injuries occurred in 17.3% (4/27) of the BTB group and 3.5% (1/29) of the HM group (P = .12). CONCLUSIONS: For young female athletes aged 20 years or younger, the BTB group had better knee instrumental stability than the HM group without range of motion loss or knee extensor muscle strength deficit. Although there was no statistical significance in terms of second ACL injury, we observed fewer graft rerupture and an increasing rate of contralateral ACL injuries in the BTB group. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

9.
Case Rep Orthop ; 2020: 7348201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158579

RESUMO

Till date, there are no clear guidelines regarding the treatment of multiple ligament knee injuries. Ligament repair is advantageous as it preserves proprioception and does not involve grafting. Many studies have reported the use of open repair and reconstruction for multiple ligament knee injuries; however, reports on arthroscopic-combined single-stage anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) repairs are scarce. In this report, we describe a case of type III knee dislocation (ACL, PCL, and medial collateral ligament (MCL) injuries) in a 43-year-old man, caused by contact while playing futsal. On the sixth day after injury, arthroscopic ACL and PCL repairs were performed with open MCL repair. The proximal lesions in the three ligaments that were injured were sutured using no. 2 strong surgical sutures. The ACL was pulled out to the lateral condyle of the femur and fixed using a suspensory fixation device. The PCL was pulled out to the medial condyle of the femur, and the MCL was pulled towards the proximal end of the femur; both were fixed using suture anchors. Early mobilization was performed, and both, clinical and imaging outcomes, were good two years after surgery.

10.
PLoS One ; 9(12): e115169, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25546433

RESUMO

Transcription factors SOX9, SOX5 and SOX6 are indispensable for generation and differentiation of chondrocytes. However, molecular mechanisms to induce the SOX genes are poorly understood. To address this issue, we previously determined the human embryonic enhancer of SOX6 by 5'RACE analysis, and identified the 46-bp core enhancer region (CES6). We initially performed yeast one-hybrid assay for screening other chondrogenic factors using CES6 as bait, and identified a zinc finger protein ZNF449. ZNF449 and Zfp449, a counterpart in mouse, transactivated enhancers or promoters of SOX6, SOX9 and COL2A1. Zfp449 was expressed in mesenchyme-derived tissues including cartilage, calvaria, muscle and tendon, as well as in other tissues including brain, lung and kidney. In limb cartilage of mouse embryo, Zfp449 protein was abundantly located in periarticular chondrocytes, and decreased in accordance with the differentiation. Zfp449 protein was also detected in articular cartilage of an adult mouse. During chondrogenic differentiation of human mesenchymal stem cells, ZNF449 was increased at an early stage, and its overexpression enhanced SOX9 and SOX6 only at the initial stage of the differentiation. We further generated Zfp449 knockout mice to examine the in vivo roles; however, no obvious abnormality was observed in skeletal development or articular cartilage homeostasis. ZNF449 may regulate chondrogenic differentiation from mesenchymal progenitor cells, although the underlying mechanisms are still unknown.


Assuntos
Condrogênese , Proteínas de Ligação a DNA/metabolismo , Animais , Cartilagem Articular/metabolismo , Linhagem Celular , Condrócitos/citologia , Condrócitos/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Estrutura Terciária de Proteína , Fatores de Transcrição SOX/genética , Fatores de Transcrição SOX/metabolismo , Dedos de Zinco
11.
Knee ; 21(6): 1151-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25245549

RESUMO

BACKGROUND: Medial collateral ligament tibial avulsion is rare. Consequently, diagnostic criteria and a treatment regimen for medial collateral ligament tibial side avulsions remain to be established. The purpose of this study is to clarify the clinical features of medial collateral ligament tibial side avulsions. METHODS: We performed a retrospective clinical and magnetic resonance imaging review of a consecutive series of 12 medial collateral ligament tibial side avulsions. All patients were treated operatively and the final diagnosis was made based on the intraoperative findings. Post-injury magnetic resonance imaging studies were reviewed to assess injury patterns with respect to the intraoperative findings. RESULTS: Eleven of 12 cases (92%) had grade III valgus laxity (unstable to valgus stress at both 0° and 30° of flexion) on an examination under anesthesia. Concomitant anterior cruciate ligament tear was noticed in all cases. Intraoperative findings were classified into 3 types depending on the location of the ruptured end of the superficial medial collateral ligament with respect to the pes anserinus tendons. Magnetic resonance imaging depicted characteristic waving ("wave sign") of the superficial layer of medial collateral ligament in all cases. CONCLUSIONS: "Wave sign" of the superficial layer of medial collateral ligament on magnetic resonance imaging is essential for diagnosing medial collateral ligament tibial side avulsions. Based on the clinical features and injury patterns, operative treatment is primarily recommended for medial collateral ligament tibial side avulsions. LEVEL OF EVIDENCE: Case series, Level IV.


Assuntos
Traumatismos em Atletas/patologia , Instabilidade Articular/patologia , Traumatismos do Joelho/patologia , Imageamento por Ressonância Magnética , Ligamento Colateral Médio do Joelho/lesões , Adolescente , Adulto , Traumatismos em Atletas/complicações , Traumatismos em Atletas/cirurgia , Feminino , Humanos , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Traumatismos do Joelho/complicações , Traumatismos do Joelho/cirurgia , Masculino , Ligamento Colateral Médio do Joelho/cirurgia , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Proc Natl Acad Sci U S A ; 110(5): 1875-80, 2013 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-23319657

RESUMO

Here we examined the involvement of Notch signaling in the endochondral ossification process, which is crucial for osteoarthritis (OA) development. Intracellular domains of Notch1 and -2 were translocated into the nucleus of chondrocytes with their differentiation in mouse limb cartilage and in mouse and human OA articular cartilage. A tissue-specific inactivation of the Notch transcriptional effector recombination signal binding protein for Ig kappa J (RBPjκ) in chondroprogenitor cells of SRY-box containing gene 9 (Sox9)-Cre;Rbpj(fl/fl) mouse embryos caused an impaired terminal stage of endochondral ossification in the limb cartilage. The RBPjκ inactivation in adult articular cartilage after normal skeletal growth using type II collagen (Col2a1)-Cre(ERT);Rbpj(fl/fl) mice by tamoxifen injection caused resistance to OA development in the knee joint. Notch intracellular domain with the effector RBPjκ stimulated endochondral ossification through induction of the target gene Hes1 in chondrocytes. Among the Notch ligands, Jagged1 was strongly induced during OA development. Finally, intraarticular injection of N-[N-(3,5-diflurophenylacetate)-L-alanyl]-(S)-phenylglycine t-butyl ester (DAPT), a small compound Notch inhibitor, to the mouse knee joint prevented OA development. The RBPjκ-dependent Notch signaling in chondrocytes modulates the terminal stage of endochondral ossification and OA development, representing an extracellular therapeutic target of OA.


Assuntos
Condrócitos/metabolismo , Osteoartrite/metabolismo , Osteogênese , Receptor Notch1/metabolismo , Receptor Notch2/metabolismo , Transdução de Sinais , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Cartilagem/patologia , Linhagem Celular , Linhagem Celular Tumoral , Condrócitos/efeitos dos fármacos , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Dipeptídeos/farmacologia , Imunofluorescência , Células HeLa , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Osteoartrite/genética , Osteoartrite/prevenção & controle , Receptor Notch1/antagonistas & inibidores , Receptor Notch1/genética , Receptor Notch2/antagonistas & inibidores , Receptor Notch2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Proteínas Serrate-Jagged , Fatores de Transcrição HES-1
13.
BMC Dev Biol ; 13: 4, 2013 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-23356643

RESUMO

BACKGROUND: Individual skeletal elements of the vertebrate limbs arise through a segmentation process introducing joints in specific locations. However, the molecular pathways controlling joint formation and subsequent joint maintenance are largely unknown. In this study, we focused on SOX11, and its contribution to the regulation of GDF5, a secreted signal necessary for proper joint formation and postnatal joint homeostasis. RESULTS: Sox11 is initially expressed broadly in the murine cartilage condensations at early stages of skeletal development, but its expression is specifically increased in the forming joint interzone as is forms. SOX11 overexpression can directly activate GDF5 expression both in vitro and in micromass cell cultures prepared from chick limb buds. Conserved SOX family binding sites are present in the 5' UTR region of the GDF5 gene and we show SOX11 can specifically bind to one of them. While misexpression of Sox11 in developing chick limbs through RCAS virus infection does not induce Gdf5 expression in ectopic locations, it does enhance its expression. To explore the roles of Sox11 in joint homeostasis, we analyzed adult knee joints in an osteoarthritis mouse model where the medial meniscus and the medial collateral ligament were removed. We also analyzed knee joints from human subjects who underwent total knee replacement surgery. We find that SOX11 is mainly expressed in the weight-bearing areas of knee joints, and its expression is decreased in degraded cartilage during progression of knee osteoarthritis in both mice and humans. CONCLUSIONS: This work implicates SOX11 as a potential regulator of GDF5 expression in joint maintenance and suggests a possible role in the pathogenesis of osteoarthritis.


Assuntos
Fator 5 de Diferenciação de Crescimento/fisiologia , Articulações/embriologia , Fatores de Transcrição SOXC/fisiologia , Regiões 5' não Traduzidas , Animais , Sequência de Bases , Cartilagem/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Fator 5 de Diferenciação de Crescimento/genética , Humanos , Camundongos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Fatores de Transcrição SOXC/genética
14.
Ann Rheum Dis ; 72(5): 748-53, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23041841

RESUMO

OBJECTIVES: To identify a new disease-modifying osteoarthritis drug (DMOAD) candidate that can effectively repair cartilage by promoting chondrogenic differentiation and halt osteoarthritis (OA) progression by suppressing aberrant hypertrophy. METHODS: We screened 2500 natural and synthetic small compounds for chondrogenic agents via four steps using the Col2GFP-ATDC5 system and identified a small thienoindazole derivative compound, TD-198946, as a novel DMOAD candidate. We tested its efficacy as a DMOAD via intra-articular injections directly into the joint space in a surgically-induced mouse model of OA both at the onset (prevention model) and 4 weeks after (repair model) OA induction. The downstream molecules were screened by microarray analysis. We further investigated the mechanism of the drug action and its molecular target using in vitro and in vivo assays. RESULTS: TD-198946 strongly induced chondrogenic differentiation without promoting hypertrophy in cell and metatarsal organ cultures. When administered directly into the joint space, TD-198946 successfully prevented and repaired degeneration of the articular cartilage. TD-198946 exerted its effect through the regulation of Runx1 expression, which was downregulated in both mouse and human OA cartilage compared with normal tissue. CONCLUSIONS: Our data suggest that TD-198946 is a novel class of DMOAD candidate, and that targeting Runx1 will provide a promising new approach in the development of disease-modifying drugs against OA.


Assuntos
Antirreumáticos/farmacologia , Condrogênese/efeitos dos fármacos , Subunidade alfa 2 de Fator de Ligação ao Core/antagonistas & inibidores , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Indazóis/farmacologia , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/prevenção & controle , Animais , Antirreumáticos/síntese química , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Diferenciação Celular/efeitos dos fármacos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Modelos Animais de Doenças , Desenho de Fármacos , Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Indazóis/síntese química , Injeções Intra-Articulares , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Camundongos , Osteoartrite do Joelho/patologia , RNA Mensageiro/metabolismo
15.
Arthritis Rheum ; 64(1): 198-203, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21905007

RESUMO

OBJECTIVE: To investigate the chondroprotective effect of cyclooxygenase 2 (COX-2) inhibition in experimental osteoarthritis (OA). METHODS: The expression of prostaglandin E2 synthetic enzymes was examined by immunostaining of tibial cartilage from mice with surgically induced knee joint instability and from OA patients undergoing total knee arthroplasty. The effect of orally administered celecoxib (10 mg/kg/day and 30 mg/kg/day) or vehicle alone in mice was examined 12 weeks after the induction of OA. To investigate the involvement of COX-1 and COX-2 in OA development, we also created the model in COX-1-homozygous-knockout (Ptgs1-/-) mice and COX-2-homozygous-knockout (Ptgs2-/-) mice. OA severity was assessed using a grading system developed by our group and by the Osteoarthritis Research Society International scoring system. RESULTS: In mouse and human OA cartilage, the expression of the inducible enzymes COX-2 and microsomal prostaglandin E synthase 1 (mPGES-1) was enhanced, while that of the constitutive enzymes COX-1, cytosolic PGES, and mPGES-2 was suppressed. Daily celecoxib treatment did not prevent cartilage degradation or osteophyte formation during OA development in the mouse model. Furthermore, neither Ptgs1-/- mice nor Ptgs2-/- mice exhibited any significant difference in OA development as compared to wild-type littermates. CONCLUSION: The two COX enzymes differ in terms of regulation of their expression during OA development. Nevertheless, experiments using inhibitor and genetic deficiency demonstrated a lack of chondroprotective effect of COX-2 inhibition in the mouse surgical OA model.


Assuntos
Artrite Experimental/enzimologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Osteoartrite do Joelho/enzimologia , Osteoartrite/enzimologia , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Administração Oral , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artroplastia do Joelho , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/cirurgia , Celecoxib , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclo-Oxigenase 1/deficiência , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/deficiência , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Oxirredutases Intramoleculares/metabolismo , Instabilidade Articular/tratamento farmacológico , Instabilidade Articular/etiologia , Masculino , Proteínas de Membrana/deficiência , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microssomos/enzimologia , Osteoartrite/patologia , Osteoartrite/prevenção & controle , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Prostaglandina-E Sintases , Joelho de Quadrúpedes/efeitos dos fármacos , Joelho de Quadrúpedes/patologia , Joelho de Quadrúpedes/cirurgia , Tíbia/efeitos dos fármacos , Tíbia/patologia , Tíbia/cirurgia
16.
Hum Mol Genet ; 21(5): 1111-23, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22095691

RESUMO

To elucidate the molecular mechanism underlying the endochondral ossification process during the skeletal growth and osteoarthritis (OA) development, we examined the signal network around CCAAT/enhancer-binding protein-ß (C/EBPß, encoded by CEBPB), a potent regulator of this process. Computational predictions and a C/EBP motif-reporter assay identified RUNX2 as the most potent transcriptional partner of C/EBPß in chondrocytes. C/EBPß and RUNX2 were induced and co-localized in highly differentiated chondrocytes during the skeletal growth and OA development of mice and humans. The compound knockout of Cebpb and Runx2 in mice caused growth retardation and resistance to OA with decreases in cartilage degradation and matrix metalloproteinase-13 (Mmp-13) expression. C/EBPß and RUNX2 cooperatively enhanced promoter activity of MMP13 through specific binding to a C/EBP-binding motif and an osteoblast-specific cis-acting element 2 motif as a protein complex. Human genetic studies failed to show the association of human CEBPB gene polymorphisms with knee OA, nor was there a genetic variation around the identified responsive region in the human MMP13 promoter. However, hypoxia-inducible factor-2α (HIF-2α), a functional and genetic regulator of knee OA through promoting endochondral ossification, was identified as a potent and functional inducer of C/EBPß expression in chondrocytes by the CEBPB promoter assay. Hence, C/EBPß and RUNX2, with MMP-13 as the target and HIF-2α as the inducer, control cartilage degradation. This molecular network in chondrocytes may represent a therapeutic target for OA.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Cartilagem/metabolismo , Condrócitos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Desenvolvimento Ósseo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Linhagem Celular Tumoral , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Humanos , Metaloproteinase 13 da Matriz/genética , Camundongos , Pessoa de Meia-Idade , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite do Joelho/genética , Regiões Promotoras Genéticas , Transcrição Gênica , Ativação Transcricional
18.
Artigo em Inglês | MEDLINE | ID: mdl-22044497

RESUMO

A young female athlete suffered from the residual instability of the knee after anterior cruciate ligament (ACL) reconstruction with hamstring autograft. The 3-dimensional (3-D) CT scan showed the "high noon" positioning of the primary femoral bone tunnel. The revision surgery with anatomic double-bundle technique was performed two years after the primary surgery and the femoral tunnels were created with the assistance of the 3-D fluoroscopy-based navigation. An arthroscopic examination confirmed the ACL graft impingement against posterior cruciate ligament (PCL) when the knee was deeply flexed. The histological analysis of the resected primary ACL graft showed local inflammatory infiltration, enhanced synovial coverage and vascularization at the impinged site. The enhanced expression of vascular endothelial growth factor (VEGF) at the impinged area when compared with non-impinged area was observed on immunohistochemical analysis. Abnormal mechanical stress by the impingement against PCL might have induced chronic inflammation and VEGF overexpression.

19.
Clin Calcium ; 21(2): 277-85, 2011 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-21289425

RESUMO

Little is known about molecular mechanism underlying osteoarthrits. Our mouse genetics approaches by mechanical stress induced OA models found that the proteinases produced during the endochondral ossification process cause cartilage degradation at the center of the joint and osteophyte formation at the periphery. At the periphery, vascularity is accessible from the synovium or tendon, which completes endochondral ossification and forms osteophytes, just as it does at the embryonic and growth plate cartilage. However, in the center, the vascularity is not accessible from the edge, so that it may end up with cartilage degradation without being replaced by bone. Molecules related to the endochondral ossification will be a therapeutic target of osteoarthritis, so our experimental mouse models are useful tools for elucidation of the molecular mechanisms.


Assuntos
Cartilagem Articular/patologia , Modelos Animais de Doenças , Osteoartrite/etiologia , Estresse Mecânico , Animais , Camundongos , Terapia de Alvo Molecular , Ossificação Heterotópica/genética , Osteoartrite/terapia , Osteófito/patologia
20.
Knee Surg Sports Traumatol Arthrosc ; 19(3): 424-31, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20814663

RESUMO

PURPOSE: The purpose of this study was to know which tunnel--the anteromedial (AM) bundle or the posterolateral (PL) bundle--should be prepared first to create the 2 femoral tunnels accurately in anatomic double-bundle (DB) anterior cruciate ligament (ACL) reconstruction. METHODS: Thirty-four patients were divided into 2 groups of 17 depending on the sequence of preparation of the 2 femoral tunnels. In group A, the AM tunnel was prepared first, whereas the PL tunnel was prepared first in group P. ACL reconstruction was performed using a three-dimensional (3-D) fluoroscopy-based navigation system to place the double femoral tunnels through an accessory medial portal. The double femoral socket positioning was evaluated by 3-D computed tomography (CT) scan image. RESULTS: The non-anatomical placement of the femoral sockets occurred in 5 patients (29%) in group A, whereas the 2 sockets were placed anatomically in all patients in group P (P < 0.05). Evaluation of the AM and the PL socket location on the 3-D CT images using the quadrant method showed more similar values to the laboratory data in a literature in group P than in group A. No complication occurred in group A, whereas complications such as socket communications or back wall blowout occurred in 5 patients (29%) in group P (P < 0.05). CONCLUSION: The sequence of creating 2 femoral tunnels through accessory medial portal affected the resultant location of the sockets and the rate of the complications. When femoral tunnels are prepared with a transportal technique, PL tunnel first technique seems to be superior to AM first technique regarding anatomic placement. However, PL tunnel first technique accompanies the risk of socket communication.


Assuntos
Ligamento Cruzado Anterior/cirurgia , Artroscopia/métodos , Imageamento Tridimensional , Articulação do Joelho/anatomia & histologia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Ligamento Cruzado Anterior/anatomia & histologia , Ligamento Cruzado Anterior/diagnóstico por imagem , Artroscópios , Estudos de Coortes , Feminino , Fêmur/anatomia & histologia , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Fluoroscopia , Humanos , Processamento de Imagem Assistida por Computador , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Adulto Jovem
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