RESUMO
BACKGROUND: Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. METHODS: Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. RESULTS: Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. CONCLUSION: The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Cério/química , Grafite/farmacologia , Nanotubos/química , Fosfatos/química , Células 3T3 , Animais , Materiais Biocompatíveis , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Regeneração Óssea , Osso e Ossos , Neoplasias da Mama/metabolismo , Proliferação de Células , Quitosana , Modelos Animais de Doenças , Feminino , Macrófagos , Camundongos , Metástase Neoplásica , Osteogênese , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio VascularRESUMO
Aseptic loosening caused by wear particles is a common complication after total hip arthroplasty. We investigated the effect of the quercetin on wear particle-mediated macrophage polarization, inflammatory response and osteolysis. In vitro, we verified that Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p-38α/ß signalling pathway by using flow cytometry, immunofluorescence assay and small interfering p-38α/ß RNA. We used enzyme-linked immunosorbent assays to confirm that the protein expression of M1 macrophages increased in the presence of Ti particles and that these pro-inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, this could be suppressed, and the protein expression of M2 macrophages was increased by the presence of the quercetin. In vivo, we revealed similar results in the mouse skull by µ-CT, H&E staining, immunohistochemistry and immunofluorescence assay. We obtained samples from patients with osteolytic tissue. Immunofluorescence analysis indicated that most of the macrophages surrounding the wear particles were M1 macrophages and that pro-inflammatory factors were released. Titanium particle-mediated M1 macrophage polarization, which caused the release of pro-inflammatory factors through the p-38α/ß signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.
Assuntos
Osteonecrose/tratamento farmacológico , Osteoprotegerina/genética , Quercetina/farmacologia , Ligante RANK/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Artroplastia de Quadril/efeitos adversos , Diferenciação Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Osteoclastos/efeitos dos fármacos , Osteonecrose/induzido quimicamente , Osteonecrose/genética , Osteonecrose/patologia , Células RAW 264.7 , Crânio/efeitos dos fármacos , Crânio/crescimento & desenvolvimento , Crânio/patologia , Titânio/efeitos adversosRESUMO
In order to improve the biocompatibility of metallic implants, bioactive components are often used as coatings so that a real bond with the surrounding bone tissue can be formed. We prepared ethyl cellulose/carbonated hydroxyapatite composite coatings (ECHCs) on Ti6Al4V substrates with carbonated hydroxyapatite coatings (CHACs) without ethyl cellulose as controls. The inorganic constituent on the CHACs and ECHCs is calcium-deficient carbonated hydroxyapatite with a flaky texture and a low degree of crystallinity. The flaky carbonated hydroxyapatite plates aggregate to form macropores with an aperture size of around 0.5-2.0 µm. The presence of ethyl cellulose provides superior morphology, contact angle, and biocompatibility characteristics. In comparison to CHACs, ECHCs exhibit a smoother, crack-free surface because the cracks are filled by ethyl cellulose. Moreover, the contact angle of ECHCs is 37.3°, greater than that of CHACs (13.0°). Surface biocompatibility was investigated by using human bone mesenchymal stem cells (hBMSCs). The attachment, spreadability, viability and proliferation of hBMSCs on ECHCs are superior to those on CHACs. Thus, the crack-free ECHCs have excellent biocompatibility and are appropriate for use as biological implants.
Assuntos
Materiais Biocompatíveis , Carbonatos/química , Celulose/análogos & derivados , Durapatita , Titânio , Ligas , Células Cultivadas , Celulose/química , Humanos , Microscopia Eletrônica de Varredura , Difração de PóRESUMO
AIM: To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA). METHODS: Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg(-1)·d(-1)) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. RESULTS: The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks. CONCLUSION: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Meniscos Tibiais/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Tiofenos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Meniscos Tibiais/patologia , Osteoartrite/etiologia , Osteoartrite/patologia , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição SOX9/metabolismo , Análise Espectral Raman , Tiofenos/administração & dosagem , Lesões do Menisco Tibial , Fatores de TempoRESUMO
AIM: To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro. METHODS: Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-κB ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNFα was analyzed with ELISA. RESULTS: Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-α production. The TNF-α level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 µmol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-α production much more efficiently in the PMMA group than in the Ti group (96 h). CONCLUSION: Calcineurin/NFAT pathway mediates wear particles-induced TNF-α release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis.
Assuntos
Calcineurina/metabolismo , Fatores de Transcrição NFATC/metabolismo , Oligopeptídeos/farmacologia , Osteoclastos/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/genética , Osteoclastos/efeitos dos fármacos , Polimetil Metacrilato/farmacologia , Ligante RANK/administração & dosagem , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Titânio/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: To investigate whether the stage of osteoarthritis (OA) progression influenced the efficacy of the third-generation bisphosphonate zoledronic acid in a rat medial meniscal tear model. METHODS: Medial meniscal tear (MMT) was surgically induced in adult male Sprague Dawley rats. Zoledronic acid (ZOL, 100 µg/kg, sc, twice a week) was administered starting immediately, early (from 4 weeks) or late (from 8 weeks) after OA induction. The degeneration of articular cartilage was evaluated with toluidine blue O staining. Subchondral bone remodeling was evaluated with X-ray micro-CT scanning. Joint pain was measured with respect to weight-bearing asymmetry. Calcitonin gene-related peptide (CGRP) expression in dorsal root ganglia (DRGs) was examined using immunofluorescence analysis. The afferent neurons in DRGs innervating the joint were identified by retrograde labeling with fluorogold. RESULTS: Progressive cartilage loss was observed during 12 weeks after OA induction. Subchondral bone remodeling manifested as increased bone resorption at early stage (4 weeks), but as increased bone accretion at advanced stages (8 weeks). Immediately and early ZOL administration significantly improved subchondral microstructural parameters, attenuated cartilage degeneration, reduced weight-bearing asymmetry and CGRP expression, whereas the late ZOL administration had no significant effects. CONCLUSION: The stage of OA progression influences the efficacy of ZOL in treating joint degeneration and pain. To obtain the maximum efficacy, bisphosphonate treatment should be initiated in rat with early stages of OA pathogenesis.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Animais , Remodelação Óssea/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/genética , Expressão Gênica/efeitos dos fármacos , Masculino , Dor/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Ácido ZoledrônicoRESUMO
With the superiority of digital imaging, conventional preoperative acetate templating is gradually being replaced by digital templating in total hip arthroplasty (THA). The purpose of this study was to assess the utility of digital templating for patients with Crowe type II and III dysplastic hips. In this study, 41 THA patients with Crowe type II or III dysplastic hips and 48 THA patients with other primary diseases were retrospectively reviewed. All patients were fitted with cementless prostheses in 2008. For the THA patients with dysplastic hips, we attempted to restore their hip centres to the position of the true acetabulum. Digital templating was the method chosen to achieve hip centre restoration. The prosthesis prediction accuracy (within ± one size using digital templating) was 20 (48.8%) for the cup size and 30 (73.2%) for the stem size. Meanwhile, for patients with other primary diseases, the accuracy for the cup size within ± one size was 34 (70.8%) and for the stem size accuracy was within ± one size in 38 (79.2%). Between the two patient groups, there was a significant difference in the predicted cup size. In patients with dysplastic hips, the low accuracy of the predicted cup size may have resulted from difficulty in predicting the vertical location of the hip centre. Despite this limitation, preoperative planning using digital templating is a convenient technique for THA patients with Crowe type II and III dysplastic hips.
Assuntos
Artroplastia de Quadril/métodos , Luxação Congênita de Quadril/cirurgia , Prótese de Quadril , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Feminino , Luxação Congênita de Quadril/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Ajuste de Prótese , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To compare rapid prototyping technology (RP tech) in revision total hip arthroplasty (RTHA) with traditional examination methods and to see how they are different in evaluating acetabular anatomy and designing surgical procedure. METHODS: From February 2014 to March 2018, 43 RTHA patients with complex acetabulum defects were enrolled in this prospective study regardless of age or gender. Incomplete and unclear data were excluded. Three types of radiographic examination were performed on each patient before the revision surgery. Four groups of evaluations were designed: (i) X-ray; (ii) computed tomography (CT-scan); (iii) RP tech; and (iv) CT-aided RP tech. Discrepancies between preoperative radiographic analysis and intra-operative findings were separately compared by a team of surgeons. Premade surgical plans based on each evaluation method were compared with the final surgical procedure. The compliance of anatomic evaluation and surgical plan-design based on 3D RP tech and traditional radiographs were ranked manually by a of team surgeons into: (i) complete accordance; (ii) general accordance; and (iii) undetermined structure/procedure. The difference in ranks between RP tech and traditional radiographic methods were analyzed with a nonparametric Kruskal-Wallis test. P < 0.05 was considered significant. Multiple adjustments were taken for the statistical tests level according to the Bonferroni method. RESULTS: For anatomic analysis, the accordance in four groups of evaluating methods differed from each other (P < 0.05) except for the comparison of RP tech and CT-aided RP tech. RP tech displayed better anatomic evaluating accuracy than traditional methods (X-ray and CT) with the "complete accordance" rates of these groups being 88.37%, 4.65% and 27.91%, respectively. But CT-aided RP tech did not improve accuracy significantly compared with using RP tech individually, although the value seems high in the CT-aided RP group with the "complete accordance" rate of 95.35%. For surgery design, RP tech significantly showed better applicable surgical design compared with X-ray and CT (P < 0.05), and the "complete accordance" rates were 88.37%, 6.98% and 23.26%, but no significant difference was observed between RP tech and CT-aided RP tech, and the "complete accordance" rate of CT-aided RP tech group was 97.67%. RP tech showed remarkable improvement in bone defect assessment and surgical plan design. CONCLUSION: Using RP technology improved both sensibility and accuracy in acetabular defect evaluation with better locating and evaluating efficiency compared with X-ray and CT-scans. It also improved surgical schedule designing in complex acetabular defecting revision surgery. In particularly complex cases, CT aided RP tech may increase the accuracy of RP tech.
Assuntos
Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Impressão Tridimensional , Falha de Prótese , Reoperação/métodos , Humanos , Estudos Prospectivos , Radiografia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To analyze the relationship between the acromial morphology and the related rotator cuff injury using a three-dimensional (3D) measurement technology. METHODS: For the present study, 226 patients (113 men and 113 women) who underwent shoulder Coarthroscopy from June 2015 to December 2019 at the Department of Orthopedics at our hospital were selected retrospectively. A total of 113 shoulder joints of age-matched healthy people were selected as the control group. A 3D model coordinate system of the shoulder was established based on CT scan images. Patients were grouped according to the condition of the rotator cuff injury during surgery. The patients whose rotator cuff tear site corresponded to the 3D osseous proliferative structure of the acromion were classified into the impingement injury group (II group). The other patients were classified into the non-impingement injury group (NII group). The acromiohumeral interval (AHI), the acromial anterior protrusion (AAP), the acromial inferior protrusion (AIP), the acromioclavicular angle (AC angle), the distance from the most medial edge of the acromial anterolateral protrusion (AALP) to the most lateral point of acromion (MLPA) (a), the distance from the most posteromedial edge of the AALP to the MLPA (b), the anteroposterior diameters of the AALP (c), and the proportion of anteroposterior diameters of AALP to the anteroposterior diameters of acromion, (c/c + d) × 100(%), were measured using the 3D shoulder model. RESULTS: The results of the intraobserver (<5%) and interobserver variability (>87%) analysis found the parameters to have high intraobserver and interobserver concordance. There were no significant differences in age among the control group, the NII group, and the II group (P = 0.8416). There were significant differences in AAP among the three groups (P = 0.0374). The results were the same for men and women, respectively. The AAP in the control group and the NII group did not show a difference, while the AAP in the II group was increased by 26.9% (P = 0.015) and 25% (P = 0.023), respectively, compared with the NII group and the control group. AHI, AIP, and AC angles did not show significant differences among the three groups (P > 0.05). The (a) and (b) of the II group were significantly larger than those of the NII group; P-values were 0.0119 and 0.0003, respectively. The (a) and (b) in patients with rotator cuff injuries were larger than in the normal population (P < 0.05). The above results were the same for men and women. This suggested that the larger width of the AALP might cause the related rotator cuff injury. The (c/c + d) in the II group was significantly larger than those in the control and the NII groups, with P-values of 0.0005 and 0.0021, respectively. The risk of rotator cuff injury due to subacromial impingement was increased when the maximum width of the medial-lateral edge of the AALP exceeded 16.8 mm (17.4 mm in men, 15.1 mm in women), the maximum width of the posterior edge of the AALP exceeded 12.9 mm (13.8 mm in men,12.7 mm in women), or the anteroposterior diameters of the AALP exceeded the anteroposterior diameters of the acromion by 33.5%. CONCLUSION: We could predict the occurrence and development of the related rotator cuff injury in symptomatic patients with specific 3D changes in their acromion and intervene in the acromion of such patients as early as possible to prevent possible rotator cuff injuries in the future.
Assuntos
Acrômio/diagnóstico por imagem , Acrômio/fisiopatologia , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/etiologia , Acrômio/cirurgia , Idoso , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Lesões do Manguito Rotador/cirurgiaRESUMO
Aseptic loosening caused by wear particles is one of the common complications after total hip arthroplasty. We investigated the effect of the recombinant protein ephB4-Fc (erythropoietin-producing human hepatocellular receptor 4) on wear particle-mediated inflammatory response. In vitro, ephrinB2 expression was analyzed using siRNA-NFATc1 (nuclear factor of activated T-cells 1) and siRNA-c-Fos. Additionally, we used Tartrate-resistant acid phosphatase (TRAP) staining, bone pit resorption, Enzyme-linked immunosorbent assay (ELISA), as well as ephrinB2 overexpression and knockdown experiments to verify the effect of ephB4-Fc on osteoclast differentiation and function. In vivo, a mouse skull model was constructed to test whether the ephB4-Fc inhibits osteolysis and inhibits inflammation by micro-CT, H&E staining, immunohistochemistry, and immunofluorescence. The gene expression of ephrinB2 was regulated by c-Fos/NFATc1. Titanium wear particles activated this signaling pathway to the promoted expression of the ephrinB2 gene. However, ephrinB2 protein can be activated by osteoblast membrane receptor ephB4 to inhibit osteoclast differentiation. In in vivo experiments, we found that ephB4 could regulate Ti particle-mediated imbalance of OPG/RANKL, and the most important finding was that ephB4 relieved the release of proinflammatory factors. The ephB4-Fc inhibits wear particle-mediated osteolysis and inflammatory response through the ephrinB2/EphB4 bidirectional signaling pathway, and ephrinB2 ligand is expected to become a new clinical drug therapeutic target.
Assuntos
Efrina-B2/metabolismo , Mediadores da Inflamação/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Receptor EphB4/farmacologia , Proteínas Recombinantes/farmacologia , Transdução de Sinais , Titânio/farmacologia , Actinas/metabolismo , Animais , Reabsorção Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Feminino , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteólise/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To assess the changes in alignment of ipsilateral knee joint after total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH). METHODS: Thirty-four patients with DDH (38 hips) who underwent THA between February and December 2008 were included in the study: 4 men and 30 women with a mean age of 56.2 years. According to Crowe classification, 11 patients were grade I, 12 were grade II, 9 were grade III, and 6 were grade IV. Computed tomography scans were performed from the anterior superior iliac spine to the tibial tubercle before surgery and at last follow-up. Femoral anteversion angle, leg lengthening, and knee alignment, including patellar tilt angle, lateral patellar displacement, and tibiofemoral rotation angle, were measured on computed tomography scans, and their relationships were analyzed. RESULTS: The mean follow-up period was 51.5 months (range, 39-70 months). There were no intraoperative fractures, and no infections occurred during the follow-up period. One patient developed deep venous thrombosis and another suffered from femoral nerve palsy. The mean preoperative Harris Hip Score was 48.9 ± 7.5 and improved to 91.2 ± 8.3 by the last follow-up (P < 0.001). There was no sign of prosthetic loosening in all hips. Postoperatively, mean leg lengthening was 26.08 ± 21.81 mm (P < 0.001), femoral anteversion decreased 9.03° ± 12.80° (P < 0.001), and patellar tilt, lateral patellar displacement, and tibiofemoral rotation increased by 3.58° ± 4.96° (P < 0.001), 1.78 ± 3.36 mm (P = 0.002), and 2.56° ± 3.37° (P < 0.001), respectively. Postoperative increase in patellar tilt and lateral patellar displacement had significant linear relationships with the decrease in femoral anteversion (r = 0.621, P < 0.001 and r = 0.437, P = 0.0037, respectively). These results revealed that patellofemoral alignment would change more with the decrease in femoral anteversion. Postoperative increase in external rotation of the tibia had significant positive linear relationships with leg lengthening (r = 0.34, P = 0.037) and the decrease in femoral anteversion (r = 0.693, P < 0.001). These results revealed that the external rotation of the proximal tibia would increase with the leg lengthening or the decrease of femoral anteversion. Postoperative changes in patellar tilt and lateral patellar displacement had no significant linear relationships with leg lengthening (P = 0.795 and P = 0.082, respectively). CONCLUSIONS: Total hip arthroplasty for DDH could induce changes in alignment of ipsilateral patellofemoral and tibiofemoral joints, with increases in patellar tilt and displacement, and increases in external rotation of the tibia. These secondary alterations still existed at medium-term follow-up after surgery, which should be considered during THA for patients with DDH. Extended follow-up is necessary to evaluate long-term changes in the knee joint.
Assuntos
Artroplastia de Quadril , Mau Alinhamento Ósseo/etiologia , Luxação Congênita de Quadril/cirurgia , Articulação do Joelho/fisiopatologia , Complicações Pós-Operatórias , Tomografia Computadorizada por Raios X , Adulto , Idoso , Mau Alinhamento Ósseo/diagnóstico por imagem , Mau Alinhamento Ósseo/fisiopatologia , Feminino , Seguimentos , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The present study investigated the role of bidirectional ephrinB2/erythropoietinproducing human hepatocellular receptor 4 (ephB4) signaling in the regulation of wear particlemediated osteoclastogenesis in vitro. Mouse bone marrow macrophages (BMMs) were induced into osteoclasts by receptor activator of nuclear factorκB ligand (RANKL, 50 ng/ml). EphB4Fc, an osteoblast membrane surface receptor (4 µg/ml), was used to stimulate the ephrinB2 ligand of osteoclasts in the presence and absence of titanium (Ti). Tartrateresistant acid phosphatase (TRAP) staining was used to detect the number of osteoclasts, and phalloidin staining was used to examine the cytoskeletons of the osteoclasts. A bone pit absorption experiment was used to measure osteoclast function. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to examine osteoclastogenesis. ELISAs were used to detect the production of inflammatory factors. The data demonstrated that Ti significantly promoted the differentiation of BMMs into mature osteoclasts in the presence of RANKL and significantly promoted expression of the ephrinB2, nuclear factor of activated Tcells 1 (NFATc1), TRAP, Fos protooncogene, AP1 transcription factor subunit (CFOS), and matrix metalloproteinase 9 (MMP9) genes. Phalloidin and TRAP staining revealed that following the addition of ephB4Fc, the number, size and cytoskeletal elements of osteoclasts were significantly decreased compared with those in the titanium particle group without ephB4Fc. Compared with the titanium particle group, the bone pit absorption experiment revealed significantly decreased absorption pit areas in the titanium particle+ephB4Fc group. The expression of the NFATc1, TRAP, CFOS and MMP9 genes was markedly decreased in the ephB4Fc group; however, the expression of the ephrinB2 gene was increased compared with the Ti particle group without ephB4Fc after 5 days. Production of inflammatory cytokines was inhibited by Ti particles through bidirectional signals. Addition of ephB4Fc inhibited the osteoclastmediated formation of Ti particles via bidirectional ephrinB2/ephB4 signaling. Activation of this bidirectional signaling pathway may be a potential clinical treatment for osteolysis surrounding prostheses.
Assuntos
Efrina-B2/metabolismo , Osteoclastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Titânio/efeitos adversos , Animais , Antígenos de Diferenciação/biossíntese , Linhagem Celular , Feminino , Camundongos , Osteoclastos/patologia , Osteólise/induzido quimicamente , Osteólise/metabolismo , Osteólise/patologia , Titânio/farmacologiaRESUMO
BACKGROUND: The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. METHODS: A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. RESULTS: Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. CONCLUSION: The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed.