Unique Characteristics of Quadriceps Muscle Morphology and Function in Older Tennis Players.

We investigated the quadriceps muscle size and quantitative characteristics in older tennis players. Thirty-eight senior tennis players (70.8 ± 5.3 years) and 38 controls (71.6 ± 5.1 years) were included. To measure the muscle size and quality, we measured muscle thickness in the rectus femoris (RF), vastus lateralis, and vastus intermedius, and muscle echo intensity in the RF and vastus lateralis using B-mode transverse ultrasound, respectively. We measured knee extension peak torque for muscle function. Muscle thickness in the RF, vastus lateralis, and vastus intermedius were significantly larger in tennis players than in controls. Tennis players had a lower echo intensity in RF and a higher knee extension peak torque compared to controls. Stepwise multiple linear regression analysis implied that echo intensity and muscle thickness were predictors of knee extension peak torque. Higher muscle quality contributes to a higher knee extension peak torque in tennis players. Playing tennis may prevent age-related muscle atrophy and maintain muscle quality in older individuals.

Shoulder and elbow pain in junior high school baseball players: Results of a nationwide survey.

BACKGROUND: Despite proposals and guidelines to prevent baseball injuries in young players by societies and organizations, many shoulder and elbow injuries continue to occur among junior high school baseball players. In order to investigate the training conditions of junior high school baseball players and the risk factors for shoulder and elbow pain in the players, we conducted a questionnaire survey among junior high school baseball players throughout the country. METHODS: The questionnaire survey was conducted among junior high school baseball players in September 2016. RESULTS: A total of 11,134 junior high school baseball players belonging to 495 teams responded to the survey. Among these, 4004 players trained every day of the week and 1151 players played baseball games every month with no off-season. Among 9752 players who did not have shoulder and/or elbow pain in the spring and summer of 2015, 19.2% of players experienced elbow pain over the course of one year, 13.6% of players experienced shoulder pain, and 28.0% complained of shoulder and/or elbow pain. The frequency of elbow pain was more than that of shoulder pain. At risk for shoulder pain were pitchers and catchers and second-year students, while risk factors for elbow pain were playing pitcher and catcher positions, pitching or throwing ≥300 balls per week, playing ≥10 games on average per month and being left-handed. CONCLUSION: Risk factors for shoulder pain were different from those for elbow pain. To prevent elbow pain, coaches should pay attention to pitchers and catchers and left-handed players and not allow players to pitch or throw ≥300 full-power balls per week or participate in ≥10 games per month. They should also pay attention to pitchers and catchers and second-year students to prevent shoulder pain. It is important for coaches to train multiple pitchers and catchers.

Shoulder and elbow pain in elementary school baseball players: The results from a nation-wide survey in Japan.

BACKGROUND: Despite recommendations on how to prevent baseball injuries in youths by the Japanese Society of Clinical Sports Medicine, shoulder and elbow pain still frequently occurs in young baseball players. We conducted a questionnaire survey among baseball players at elementary schools across the country to understand the practice conditions of players, examining the risk factors of shoulder and elbow pain in baseball players. METHODS: The questionnaire survey was conducted among elementary school baseball players as members of the Baseball Federation of Japan in September 2015. RESULTS: A total of 8354 players belonging to 412 teams (average age: 8.9) responded to the survey. Among 7894 players who did not have any shoulder and/or elbow pain in September 2014, elbow pain was experienced in 12.3% of them, shoulder pain in 8.0% and shoulder and/or elbow pain in 17.4% during the previous one year. A total of 2835 (39.9% of the total) practiced four days or more per week and 97.6% practiced 3 h or more per day on Saturdays and Sundays. The risk factors associated shoulder and elbow pain included a male sex, older age, pitchers and catchers, and players throwing more than 50 balls per day. CONCLUSIONS: It has been revealed that Japanese elementary school baseball players train too much. Coaches should pay attention to older players, male players, pitchers and catchers in order to prevent shoulder and elbow pain. Furthermore, elementary school baseball players should not be allowed to throw more than 50 balls per day. STUDY DESIGN: Retrospective cohort study.

Anatomical characteristics of the accessory antero-lateral talar facet.

BACKGROUND: We examined the anatomical features of the accessory antero-lateral talar facet (AALTF) in adults. METHODS: The sample comprised 44 feet (male: 10 cadavers and 20 feet; female: 12 cadavers and 24 feet) obtained from 22 cadavers used for systemic autopsy. The mean age was 86.5 years. The talus and calcaneus were obtained from the autopsy cadavers, and the soft tissue was surgically removed from the bone. The talus and calcaneus were then separated and their anatomical features were observed. RESULTS: The AALTF was identified in 11 of 44 (25 %) feet. The presence or absence of the AALTF and calcaneal facet opposing the AALTF were classified into four groups: (1) joint type with articular cartilage on both the talus and calcaneus; (2) talar type with articular cartilage on the talus only; (3) calcaneal type with articular cartilage on the calcaneus only; and (4) non-joint type with no articular cartilage on either the talus or calcaneus. CONCLUSIONS: When the AALTF is present, the talus comes into contact with the calcaneus, and thus even slight changes around the talus and calcaneus can easily cause impingement.

Effects of tofacitinib on nucleic acid metabolism in human articular chondrocytes.

OBJECTIVE: In our previous screening of chondrocyte protein profiles, the amount of adenosine monophosphate deaminase (AMPD) 2 was found to be decreased by tofacitinib. Extending the study, here we confirmed the decrease of AMPD2 by tofacitinib and further investigated effects of tofacitinib on purine nucleotide metabolism. METHODS: Human articular chondrocytes and a chondrosarcoma cell line: OUMS-27 were stimulated with tofacitinib. Then the levels of AMPD2 and its related enzymes were investigated by Western blot. The levels of AMP and adenosine were assessed by mass spectrometry. RESULTS: We confirmed the significant decrease of AMPD2 by tofacitinib in chondrocytes (p = 0.025). The levels of adenosine kinase and 5'-nucleotidase were decreased in chondrocytes, although they did not meet statistical significance (p = 0.067 and p = 0.074, respectively). The results from OUMS-27 were similar to those from the chondrocytes. The cellular adenosine levels were significantly decreased by tofacitinib in OUMS-27 (p = 0.014). The cellular AMP levels were increased, although they did not meet statistical significance in OUMS-27 (p = 0.066). CONCLUSION: Our data indicate that tofacitinib increases the cellular levels of adenosine, which is known to have anti-inflammatory activity, through the downregulation of AMPD2. This would be a novel functional aspect of tofacitinib.

Secretion of inflammatory factors from chondrocytes by layilin signaling.

Layilin (LAYN) is thought to be involved in reorganization of cytoskeleton structures, interacting with merlin, radixin, and talin. Also, LAYN is known to be one of the receptors for hyaluronic acid (HA). In rheumatoid arthritis (RA), inflammatory cytokines like tumor necrosis factor α (TNF-α) have been known to play pathological roles. HA with low molecular weight is speculated to exacerbate inflammation in RA. In this context, differences of quantity and functions of HA receptors would affect the severity of inflammation in RA. Chondrocytes, which play critical roles in maintaining articular cartilage and are affected in RA, express at least kinds of HA receptors like CD44 and LAYN. However, roles and regulation of LAYN in articular chondrocytes have been poorly understood. To clarify regulation of LAYN in chondrocytes, we here investigated whether TNF-α affected expression levels of LAYN in human articular chondrocytes. Next, to clarify LAYN-specific roles in chondrocytes, we investigated whether binding of antibodies to the extracellular domain of LAYN affected secretion of inflammatory cytokines using a chondrosarcoma cell line. As a result, we found that TNF-α up-regulated expression levels of LAYN in the chondrocytes. Further, the LAYN signaling was found to enhance secretion of inflammatory factors, IL-8 and complement5 (C5)/C5a, from the cells. Our results indicate that LAYN would be involved in the enhancement of inflammation and degradation of cartilage in joint diseases such as RA and OA.

The DNA repair enzyme apurinic/apyrimidinic endonuclease (Apex nuclease) 2 has the potential to protect against down-regulation of chondrocyte activity in osteoarthritis.

Apurinic/apyrimidinic endonuclease 2 (Apex 2) plays a critical role in DNA repair caused by oxidative damage in a variety of human somatic cells. We speculated that chondrocyte Apex 2 may protect against the catabolic process of articular cartilage in osteoarthritis (OA). Higher levels of Apex 2 expression were histologically observed in severely compared with mildly degenerated OA cartilage from STR/OrtCrlj mice, an experimental model which spontaneously develops OA. The immunopositivity of Apex 2 was significantly correlated with the degree of cartilage degeneration. Moreover, the OA-related catabolic factor interleukin-1ß induced the expression of Apex 2 in chondrocytes, while Apex 2 silencing using small interfering RNA reduced chondrocyte activity in vitro. The expression of Apex 2 in chondrocytes therefore appears to be associated with the degeneration of articular cartilage and could be induced by an OA-related catabolic factor to protect against the catabolic process of articular cartilage. Our findings suggest that Apex 2 may have the potential to prevent the catabolic stress-mediated down-regulation of chondrocyte activity in OA.

Effects of sulfasalazine and tofacitinib on the protein profile of articular chondrocytes.

OBJECTIVE: Sulfasalazine (SSZ) and tofacitinib are effective for treating rheumatoid arthritis, however, their effects on chondrocytes have not been fully understood. We here tried to elucidate their effects on chondrocyte proteins. METHODS: We treated chondrocytes from five osteoarthritis patients with IL-1ß, IL-1ß+ SSZ, IL-1ß+ tofacitinib, SSZ alone, and tofacitinib alone. Then, we compared protein profiles of the chondrocytes using two-dimensional differential gel electrophoresis. Further, we identified altered proteins by mass spectrometry. RESULTS: Out of 892 detected protein spots, the IL-1ß stimulation changed intensity of 43 spots more than 1.3-fold or less than 1/1.3-fold significantly. SSZ suppressed the IL-1ß-induced intensity alteration in 16 (37%) out of the 43 protein spots. Tofacitinib suppressed the IL-1ß-induced alteration in 4 (9.3%) out of the 43 spots. The production of AMP deaminase 2 and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 were increased by IL-1ß and the increase was suppressed by SSZ and by tofacitinib. SSZ alone altered intensity of 273 (31%) out of the 852 spots significantly, whereas tofacitinib alone altered intensity of only 24 (2.7%) out of them. CONCLUSION: SSZ and, to lesser extent, tofacitinib suppress the effects of IL-1ß on the protein profiles of chondrocytes. Our data would promote understanding of effects of the drugs on chondrocytes.

Newly developed anatomical and functional ligament reconstruction for the Lisfranc joint fracture dislocations: a case report.

A 15-year-old male complained of pain in the left foot that occurred when changing direction while running and at presentation, he had difficulty in walking due to pain and swelling. Plain X-ray of the foot revealed a Myerson Type B2 Lisfranc fracture dislocation, and 3-D computed tomography (CT) revealed proximal fractures of the 2nd-4th metatarsals. The Lisfranc ligament was anatomically reconstructed using a graft of the gracilis tendon. During aftercare, partial weight bearing was permitted at 6 weeks postoperatively and full weight bearing at 8 weeks postoperatively. The patient resumed sporting activities 3 months postoperatively. A plain X-ray taken 12 months postoperatively showed favorable joint congruency, and the patient scored 100 points on the Japanese Society for Surgery of the Foot standard rating system midfoot scale. Our anatomical ligament reconstruction is a useful new method of anatomical reduction and maintenance, and it shortens the duration of aftercare.

Anatomical considerations for reconstruction of the Lisfranc ligament.

BACKGROUND: The Lisfranc ligament is important in supporting the arch of the foot. Injury to this ligament causes pain and deformity of the foot. METHODS: We studied the Lisfranc ligament and its surrounding anatomical structures in detail, and examined the route for reconstruction and the thickness of the ligament for optimum reconstruction. 78 feet of 39 cadavers were used for systematic dissection. Of the cadavers 17 were males and 22 were females; their ages ranged from 60 to 99 years (mean age 84.5 years). RESULTS: The Lisfranc ligament is a fasciculated interosseous ligament that binds the lateral surface of C1 and the medial surface of M2. It has one to four fasciculi; the mean number of fasciculi is 2.0 and the cross-sectional area is 88 mm(2). The ideal reconstruction is such that the center of the ligament is positioned 5.9 mm distally from the C2-M2 joint surface on M2, and at a position 8.6 mm centrally from the C1-M1 joint surface on C1. The reconstruction would also be ideal if positioned at the same level as the C2-M2 joint surface on C1, horizontal to the plantar surface from the medial surface of C1 toward M2. This is the route for anatomical reconstruction of the Lisfranc ligament. CONCLUSION: Our results reveal some important aspects of anatomical and physiological ligament reconstruction.

Ultrasonographic observation of the healing process in the gap after a Ponseti-type Achilles tenotomy for idiopathic congenital clubfoot at two-year follow-up.

BACKGROUND: Ponseti management usually requires Achilles tenotomy during the final stage of serial casting. However, we lack a good understanding of the sequential tendon healing process after tenotomy in the Ponseti bracing protocol. The purpose of this study was to clarify the ultrasonographic process of tendon healing in the gap for up to two years after Ponseti-type Achilles tenotomy in patients with clubfeet. METHODS: We conducted an ultrasonographic study to clarify the sequential changes in gap healing for up to two years after tenotomy. The subjects were 23 patients with 33 clubfeet. Achilles tenotomy was performed at mean 10.4 (8-16) weeks after birth. Dynamic and static ultrasonography was performed before tenotomy and at 1, 2, 3, 4, 6, 8, and 12 weeks as well as at 4, 6, 12, 18, and 24 months after tenotomy. RESULTS: Continuity and gliding were noted within four weeks. The united portion continued to thicken for up to three months after tenotomy. Starting from the fourth month, the healed portion began to lose its thickness, and this process continued into the sixth month. At one year, the thickness of the tendon did not differ much from that of the tendon on the opposing foot. In cases where patients had clubfoot on both feet and underwent simultaneous tenotomies, measurement of the tendons could not be accurately compared. At two years after tenotomy, slight irregularity of the internal structure persisted when compared with the unaffected foot. In addition, clinical and X-ray findings were evaluated simultaneously, and no recurrence was confirmed. CONCLUSIONS: To our knowledge, our results are the first to describe the process of gap healing in the tendon after tenotomy up to and beyond two years, as recommended in the Ponseti bracing protocol. Level of evidence IV.

Effect of Achilles tenotomy on congenital clubfoot-associated calf-muscle atrophy: an ultrasonographic study.

BACKGROUND: The Ponseti method for treating congenital clubfoot requires Achilles tenotomy to be performed toward the end of serial casting. However, it remains unclear if Achilles tenotomy has a negative effect on clubfoot-associated calf-muscle atrophy. We therefore investigated this issue by ultrasonographic examination. MATERIALS AND METHODS: We studied 36 patients with congenital clubfoot who were treated with the Ponseti method and underwent Achilles tenotomy. Only unilateral cases were evaluated to enable comparison of the severity of atrophy and its changes over time between affected and unaffected sides. Tenotomy was performed at a mean age of 10.2 weeks after birth (range 8-16 weeks). The transverse and anteroposterior diameters of the calf muscles on the unaffected and affected sides were measured ultrasonographically by two examiners. The mean observation period was 27 months (range 24-34 months). Measurements were performed within 6 months after tenotomy, between 7 and 17 months after tenotomy, and at the final assessment. Differences between the diameters of the affected and unaffected sides at each time point, and changes in the diameters over time were determined. The data were analyzed by use of one-way ANOVA and repeated-measures ANOVA. RESULTS: Tendon healing and gliding were achieved in all cases. There were significant differences between the diameters of the unaffected and affected sides at all measurement points (transverse p < 0.005, anteroposterior p < 0.01). The diameters of calf muscles on both sides increased significantly over time (p < 0.0001). The patterns of change in diameter were similar on both sides. CONCLUSION: The transverse and anteroposterior diameters of the calf muscles differed significantly between the affected and unaffected sides after Achilles tenotomy, but there were no significant differences in changes over time. These results suggest that Achilles tenotomy had no negative short-term effects on calf-muscle atrophy associated with clubfoot.

Layilin, a talin-binding hyaluronan receptor, is expressed in human articular chondrocytes and synoviocytes and is down-regulated by interleukin-1ß.

OBJECTIVE: Layilin (LAYN), a 55-kDa transmembrane protein with homology to C-type lectins, has been identified as a receptor of hyaluronan (HA). Interestingly, LAYN does not share any sequence homology with CD44, a primary HA receptor. The primary aim of our study was to examine the expression and potential function of LAYN in human articular chondrocytes and synoviocytes. METHODS: Samples were obtained from patients undergoing joint arthroplasty. Cells were grown in vitro, then stimulated with interleukin (IL)-1ß or tumor necrosis factor alpha (TNFα) for 24 h and the expression of LAYN was analyzed. To assess the function of LAYN, we transfected chondrocytes with siRNA against LAYN, treated them with HA and IL-1ß, and then analyzed the production of matrix metalloproteinase (MMP)-1 and MMP-13 in the treated chrondrocytes. RESULTS: The results showed that LAYN was constitutively expressed in human articular chondrocytes and synoviocytes and that IL-1ß significantly suppressed the expression of LAYN in these cells. HA repressed IL-1ß-induced MMP-1 and MMP-13 production in chondrocytes, but this was significantly abrogated in chondrocytes transfected with siRNA against LAYN. CONCLUSIONS: Our results show that human chondrocytes express LAYN, a novel HA receptor, and that LAYN may contribute to the regulation of HA functions in the arthritic condition. Further investigation of the HA receptor may lead to the development of novel therapeutics to regulate HA signaling in inflammatory arthritis.

Applicability of the seated step test for assessing thigh muscle sarcopenia in older individuals.

Assessment of lower limb muscle mass and related functions in older individuals is important because of their essential role in maintaining locomotion and activities of daily living. Therefore, a simple and reliable method for assessing these parameters should be established. The seated step test is easy and safe and can be used to assess lower limb agility; however, its relationship to skeletal muscle mass and function remains unknown. The present study aimed to investigate the relationships between the seated step test and lower limb muscle mass and function. For the analysis, we included 85 participants aged 73.1 ± 6.0 years. The participants performed an alternate up-down leg step test for 10 s while seated in a chair. Lower limb muscle mass was measured using bioimpedance analysis. Skeletal muscle mass index (SMI) was calculated using the following equation: lower limb muscle mass (kg) / height2 (m2). As the muscle functional parameters, we measured the isometric knee extension peak torque (KEPT), knee flexion peak torque (KFPT), and rate of torque development (RTD) for isometric knee extension in all participants. The seated step test score had a significant relationship with KEPT, KFPT, and SMI, but not with RTD. In the single regression analysis, the seated step test significantly predicted KEPT, KFPT, and SMI. These results suggest that up-down seated step test can be a reliable method to estimate lower limb muscle size and function in older individuals.

Overexpression of SPACIA1/SAAL1, a newly identified gene that is involved in synoviocyte proliferation, accelerates the progression of synovitis in mice and humans.

OBJECTIVE: To identify novel genes associated with dysregulated proliferation of activated synovial fibroblasts, which are involved in arthritic joint destruction. METHODS: We performed transcriptome analysis to identify genes that were up-regulated in the foot joints of mice with collagen-induced arthritis (CIA). The effect of candidate genes on proliferation of synovial fibroblasts was screened using antisense oligodeoxynucleotides and small interfering RNAs (siRNAs). We characterized the expression and function of a novel gene, synoviocyte proliferation-associated in collagen-induced arthritis 1 (SPACIA1)/serum amyloid A-like 1 (SAAL1) using antibodies and siRNA and established transgenic mice to examine the effect of SPACIA1/SAAL1 overexpression in CIA. RESULTS: Human and mouse SPACIA1/SAAL1 encoded 474 amino acid proteins that shared 80% homology. SPACIA1/SAAL1 was primarily expressed in the nucleus of rheumatoid arthritis (RA) synovial fibroblasts and was highly expressed in the hyperplastic lining of inflamed synovium. In addition, its expression level in RA- or osteoarthritis (OA)-affected synovial tissue was positively correlated with the thickness of the synovial lining. Furthermore, SPACIA1/SAAL1 siRNA inhibited the proliferation of synovial fibroblasts, especially tumor necrosis factor α-induced synovial fibroblasts, by blocking entry into the S phase without inducing apoptosis. Finally, transgenic mice overexpressing SPACIA1/SAAL1 exhibited early onset and rapid progression of CIA. CONCLUSION: These results suggest that SPACIA1/SAAL1 is necessary for abnormal proliferation of synovial fibroblasts and its overexpression is associated with the progression of synovitis in mice and humans. Thus, therapy targeting SPACIA1/SAAL1 might have potential as an inhibitor of synovial proliferation in RA and/or OA.

Outcome of medial displacement calcaneal osteotomy for correction of adult-acquired flatfoot.

BACKGROUND: The results of medial displacement calcaneal osteotomy (MDCO) with flexor digitorum longus (FDL) tendon transfer were reviewed, as well as postoperative radiographic changes, to determine quantitative x-ray-based indications for MDCO with FDL tendon transfer in cases of adult-acquired flatfoot. MATERIALS AND METHODS: Twenty-five patients, ages 42 to 71 years, underwent MDCO with FDL tendon transfer for stage II posterior tibial tendon dysfunction. Follow-up was 2.6 to 10.2 years. Preoperative and postoperative Japanese Society for Surgery of the Foot (JSSF), Foot Function Index, and SF-36 scores and physical and radiographic findings were compared. Eight measures of foot alignment were obtained from weight-bearing radiographs at 3, 6, 9, and 12 months after surgery and every 6 months thereafter. Differences in scores and values over time were analyzed statistically. RESULTS: Average JSSF scores improved from 59 preoperatively to 91.3 postoperatively (p < .001). The only x-ray parameters that improved significantly and showed maintenance of the surgical correction were the lateral talometatarsal (LTMT) and tibiocalcaneal (TBC) angles. With preoperative LTMT and TBC angles of >25° and >15°, respectively, correction was inadequate. CONCLUSIONS: It was concluded that indications for MDCO with FDL tendon transfer in cases of adult-acquired flatfoot are a preoperative LTMT angle of <25° and hindfoot coronal alignment (TBC angle) of <15°.

Prostaglandin EP2 receptor signalling inhibits the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes.

OBJECTIVES: Matrix metalloproteinase (MMP) 13 is a pathogenic collagenase that causes cartilage destruction and plays a leading role in causing osteoarthritis. This study focused on 114 genes that are differentially expressed between intact and damaged osteoarthritis cartilage, in order to determine which molecules are involved in suppressing MMP-13 expression. METHODS: MMP-13 concentrations were measured in the supernatant of human osteoarthritis chondrocyte cultures transfected with small interfering RNA (siRNA) against the 114 genes. MMP-13 levels changed most dramatically in response to siRNA against prostaglandin EP2 receptor. The authors performed further measurements of MMP-13 production in osteoarthritis chondrocytes stimulated by the EP2 agonist butaprost in the presence or absence of interleukin-1ß (IL-1ß) and/or cyclooxygenase-2 (COX-2) inhibitor. They also assessed the effect of butaprost on chondrocyte viability, and investigated the involvement of the cAMP-protein kinase A (PKA) pathway on EP2 signalling using inhibitors. Cartilage-related gene expression was examined in chondrocytes treated with butaprost. The authors also investigated which E series of prostaglandin (EP) receptors are expressed in osteoarthritis cartilage. RESULTS: MMP-13 messenger RNA expression was significantly affected by two molecules, EP2 receptor and SLC14A1, a urea transporter. In IL-1ß-treated osteoarthritis chondrocytes, butaprost suppressed MMP-13 production, which was further decreased by COX-2 inhibitor. EP2 signalling downregulated MMP-13 mRNA expression via the cAMP-PKA pathway without affecting cell viability. Although EP2 signalling enhanced IL-6 expression, the expressions of several catabolic factors (MMP-1, MMP-3, MMP-13, ADAMTS5, IL-1ß and tumour necrosis factor alpha) were inhibited. EP2 receptor was the major EP receptor in osteoarthritis cartilage. CONCLUSION: The results suggest that EP2 signalling has 'anti-catabolic' effects in osteoarthritis chondrocytes.

Arthritogenicity of annexin VII revealed by phosphoproteomics of rheumatoid synoviocytes.

OBJECTIVE: To identify novel proteins involved in the pathogenesis of rheumatoid arthritis (RA) and to characterise the identified proteins based on pathogenic and therapeutic aspects. METHODS: The authors applied differential phosphoproteomic analysis to articular synoviocytes between RA and osteoarthritis (OA) to identify proteins differently phosphorylated between RA and OA. Focusing on annexin VII (Anx7), one of the highly phosphorylated proteins in RA, the authors prepared Anx7-transgenic C57BL/6 (Anx7-Tg-B6) mice to evaluate their susceptibility to collagen-induced arthritis (CIA). In addition, the authors examined the effect of anti-Anx7 antibodies (Abs) on CIA and serum levels of cytokines in wild-type DBA/1J mice, which are known to be susceptible to CIA, and in Anx7-Tg-B6 mice. In vitro, the authors examined the effect of the Anx7 knockdown by small interfering RNA on the secretion of cytokines in rheumatoid synoviocytes and the human synovial sarcoma cell line SW982. RESULTS: The Anx7 transgene altered the CIA-resistant B6 mice to CIA-susceptible ones. The Abs treatment suppressed CIA even in the wild-type DBA/1J mice. The serum levels of cytokines including interleukin 6 (IL-6) and TNFα were not altered by the Abs treatment in vivo. On the other hand, the knockdown of Anx7 by small interfering RNA caused downregulation of IL-8 secretion in vitro. CONCLUSIONS: These results indicate that Anx7 participates in the pathogenesis of RA partly through the secretion of IL-8. The study data have demonstrated the pathogenic roles and therapeutic significance of Anx7 in RA for the first time.

Long-term assessment of morphological, functional, and quantitative parameters of skeletal muscle in older patients after unilateral total hip arthroplasty.

Total hip arthroplasty (THA) is performed for pain relief in patients with osteoarthritis of the hip joint. After THA, patients may recover muscle mass and physical function. Muscle quality is the main parameter used to indicate intramuscular fat content, and it is related with muscle function in older individuals. However, how THA affects muscle quality, as determined by echo intensity (EI), is not well understood. The purpose of this study was to determine the long-term characteristics of EI, muscle quantity, muscle function, and physical functions in the patients with THA surgery. In order to achieve the purpose, we performed two comparison. First, we compared muscle EI, quantity and function in operated leg with unoperated legs in the same patients and with the legs of healthy adults (i.e., both unoperated legs). Second, we compared physical functional tests between THA patient and age and body composition matched controls. Twenty-two older individuals (age: 67.1 ± 5.3 years, height: 160.9 ± 7.1 cm, body mass: 62.6 ± 16.1 kg) who underwent unilateral THA several (5.2 ± 3.1) years ago (THA group) and 22 healthy controls with matching age and body composition (age: 68.3 ± 4.4 years, height: 160.3 ± 7.9 cm, body mass: 61.7 ± 7.8 kg) (CON group) participated in this case-control study. EI, an index of muscle quality, and muscle thickness (MT), an index of muscle quantity, were measured from B-mode transverse images of the rectus femoris obtained through ultrasound. The maximal isometric knee extension torque was measured in both the operated and unoperated legs in the THA group and in the right leg in the CON group (control leg); physical function tests, such as sit-to-stand, walking speed, hip adduction, and abduction torque assessments, were performed in both groups. MT and maximal isometric knee extension torque in operated leg were not different with unoperated, and control legs; the EI in the operated leg was significantly higher than that in the control leg (106.9 ± 16.9 vs. 92.4 ± 21.0 a.u., P < 0.05). The THA group demonstrated slower walking speed and lower hip abduction torque than the CON group (walking speed: 1.3 ± 0.2 vs. 1.5 ± 0.2 m/s; hip abduction torque 1.2 ± 0.3 vs. 1.5 ± 0.5 Nm/kg, P < 0.05). Several years after THA, the operated legs completely recovered the same level of muscle quantity as that in healthy participants but with lower muscle quality and hip joint function. These defects may be associated with locomotive dysfunction in older THA patients.

Administration of granulocyte colony-stimulating factor facilitates the regenerative process of injured mice skeletal muscle via the activation of Akt/GSK3alphabeta signals.

Effects of administration of granulocyte colony-stimulating factor (G-CSF) on the regeneration of injured mammalian skeletal muscles were studied in male C57BL/6J mice. Muscle injury was induced by injection of cardiotoxin (CTX) into tibialis anterior muscles bilaterally. G-CSF was administrated for 8 consecutive days from 3 days before and 5 days after the injection. Significant decreases of wet weight and protein content were noted in the necrotic muscle with CTX injection. A large number of the regenerating fibers having central nucleus were observed 7 days after the injection. The regeneration of injured muscle was further facilitated by the G-CSF treatment. Population of Pax7-positive nuclei was increased by the G-CSF treatment at day 7. Phospho-Akt and phospho-glycogen synthase kinase 3alphabeta (GSK3alphabeta) signals were also activated by G-CSF-administrated group during the regenerative process. It was suggested that G-CSF treatment may facilitate the regeneration of injured skeletal muscles via the activation of Akt/GSK3alphabeta signals.