Suppression of CRLF1 promotes the chondrogenic differentiation of bone marrow-derived mesenchymal stem and protects cartilage tissue from damage in osteoarthritis via activation of miR-320.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disease, and is hard to be cured at present. Cytokine receptor-like factor 1 (CRLF1) has been identified as an upregulated gene in OA cartilage. However, the precise identities and functions of CRLF1 in OA progression have remained to be fully elucidated. METHODS: We used a murine model of injury-induced OA (destabilization of medial meniscus, DMM) and BMSCs to investigate the specific biological functions and mechanisms of CRLF1. RESULTS: We found that CRLF1 was significantly increased in the DMM surgery-induced OA model and was down-regulated during chondrogenic differentiation of BMSCs. Luciferase reporter assays showed that CRLF1 was a direct target of miR-320 in BMSCs. miR-320 can reverse the effect of CRLF1 on cell proliferation, apoptosis and chondrogenic differentiation of BMSCs. Furthermore, knockdown of CRLF1 or over-expression of miR-320 can inhibit the apoptosis of primary chondrocytes. CONCLUSION: Suppression of CRLF1 promotes the chondrogenic differentiation of BMSCs and protects cartilage tissue from damage in osteoarthritis via activation of miR-320.

Early Patellofemoral Function of Medial Pivot Prostheses Compared with Posterior-Stabilized Prostheses for Unilateral Total Knee Arthroplasty.

OBJECTIVE: To systematically evaluate the patellofemoral joint design of medial pivot prosthesis, which incorporates a variety of "patella-friendly" design features, by comparing clinical and radiographic results with another prosthesis. METHODS: All consecutive patients who underwent unilateral total knee arthroplasty (TKA) with medial pivot prosthesis (Group MP, 126 cases) between September 2016 and April 2018 were enrolled in this retrospective study. For each patient reviewed, a control patient was matched, according to age, gender, side, body mass index (BMI), preoperative range of motion (ROM), and operating period, who had received primary unilateral TKA with a conventional posterior-stabilized prosthesis at the same period as the study group (Group PS, 126 cases). All patients underwent at least 1-year follow-up. At the preoperative and final follow-up periods, data on the Knee Society Score (KSS) score, WOMAC score, Kujala score, and ROM were collected. Merchant views were taken with the knee flexion at 30°, 60°, and 90° to measure patella shift and tilt. Preoperative posterior condylar angle (PCA) was also measured. Postoperative complications, including anterior knee pain, maltracking, patellar clunk or crepitus (PCC), were evaluated. RESULTS: There were no significant differences in the demographics or clinical characteristics between the two groups. No statistically significant difference was identified in the KSS total score, including knee score and function score, or in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between the two groups after the operation. We found statistically significant differences in the postoperative Kujala scores and the ROMs between the two groups. The mean Kujala score in group MP was better than in group PS (MP 77.16 ± 3.80 vs PS 75.97 ± 4.06, P < 0.05), while the ROM in group PS was significantly higher than in group MP (MP 122.24° ± 4.45° vs PS 123.78° ± 6.05°, P < 0.05). Simultaneously, the preoperative/postoperative Kujala score improvement in group MP was observed to be significantly larger than in group PS (MP 27.82 ± 5.31 vs PS 26.17 ± 4.89, P < 0.05), but the average ROM improvement in group PS was significantly greater than in group MP (MP 19.00° ±9.90° vs PS 21.57° ± 9.62°). In the 90° Merchant view, the mean patella tilt of group MP was statistically smaller than that of group PS (MP 4.21° ± 1.62° vs PS 4.74° ± 1.95°, P < 0.05), and the average patella tilt change in group MP was significantly greater than in group PS (MP -3.8° ± 1.43° vs PS -3.23° ± 1.33°, P < 0.05). Preoperative PCA did not show significant differences between the two groups. Two cases of PCC and three cases of anterior knee pain were noted in group MP, and nine cases and six cases, respectively, were observed in group PS. The incidence of PCC was significantly lower in group MP (1.6% vs 7.1%, P < 0.05). There was no significant difference in follow-up time between the two groups. CONCLUSION: The medial pivot prosthesis could achieve satisfactory outcomes with better patellofemoral performance attributed to its "patella-friendly" design characteristics compared to the conventional posterior-stabilized prosthesis.

Comparison of core decompression and porous tantalum rod implantation with conservative treatment for avascular necrosis of the femoral head: A minimum 18 month follow-up study.

Porous tantalum rod implantation is a novel surgical method that is used to treat avascular necrosis (AVN) of the femoral head (hip). In the present study, the results of core decompression and tantalum rod implantation were compared with non-surgical treatment for AVN, and the survivorship of the femoral head was evaluated. In total, 60 patients with AVN femoral head were recruited and analysed. Non-surgical treatment was selected by 30 patients (41 hips), 7 with a Ficat score of I and 23 with a score of II. Non-surgical treatment included celecoxib, salvia miltiorrhiza and tetramethylypyrazine and a reduction in weight-bearing activities. Surgical treatment and porous tantalum rod implantation were selected by 30 patients (41 hips), 10 with a Ficat score of I and 20 with a score of II. After follow-up (average: 33.5 months), patients were evaluated by assessing post-operative complications, radiology, hip survivorship and Harris hip score. In the surgical group, pre-operative symptoms were significantly alleviated. No complications, including infection, delayed healing or fractures were reported. Final follow-up rates of femoral head survivorship were 4.9% in the non-surgical group and 36.7% in the surgical group. The Harris hip score was significantly improved following surgery when compared with non-surgical treatment (P<0.05). The results indicated that core decompression and porous tantalum rod implantation are beneficial short- and mid-term treatment methods for AVN of the femoral head.

Reconstruct large osteochondral defects of the knee with hIGF-1 gene enhanced Mosaicplasty.

OBJECTIVE: To investigate a compound technique including gene therapy, injectable tissue engineering and Mosaicplasty to reconstruct large osteochondral defect. METHODS: Plasmid vector containing hIGF-1 cDNA was created and transfected into BMSCs in vitro with FuGene6. After gene expression determination, cells were mixed with calcium alginate gel. Osteochondral defects were created on the femoral condyle of goats in a diameter of 6mm. Osteochondral plugs were harvested from the intertrochlea groove and pressed into the recipient sites in a mosaic mode. Gene modified BMSCs-scaffold complex was applied to fill the residual defects. Control groups were also set up. At 4 and 16 weeks, specimens were investigated in gross and under microscopy, electromicroscopy and MRI detection. RESULTS: hIGF-I gene was expressed effectively with the peak concentration at 34.75 ng/ml. Subchondral bone and cartilage were integrated well in gene enhanced Mosaicplasty group. The reconstructed tissue filled up the gaps between columns, which appeared better than other groups. The regenerated cartilage was integrated with neighbor tightly in regular arrange. Extracellular matrix distributed evenly and deeply stained by alcian blue. Quantitative histologic assessments showed higher score in gene enhanced Mosaicplasty group. Glycosaminoglycan assay revealed no difference between groups involving Mosaicplasty. MRI analysis demonstrated the healing process between the subchondral bone other than control groups. CONCLUSIONS: hIGF-I gene enhanced tissue engineering can modify the outcome of Mosaicplasty to reconstruct large osteochondral defects in weight-bearing region.

Effects of antisense transforming growth factor-beta1 gene transfer on the biological activities of tendon sheath fibroblasts.

Recent studies have shown the importance of transforming growth factor-beta (TGF-beta) in flexor tendon wound healing. Decreased adhesion formation and increased range of motion after the administration of TGF-beta antibodies after tendon repair have been shown. But TGF-beta antibodies have a short biologic half-life, and continuous supplementation of exogenous TGF-beta antibodies is not practical. Transfer of growth factor genes to tenocytes provides an alternative to protein therapeutics, and a gene therapy approach will prolong the availability of therapeutic proteins.We investigated the biological activities effects of rabbit tendon sheath fibroblasts transfected by antisense TGF-beta1 gene. Tendon sheath fibroblasts were isolated from New Zealand white rabbits and transfected by antisense TGF-beta1 gene with Lipofectin (Invitrogen, Carlsbad, California). Reverse transcription polymerase chain reaction was used to measure collagen I, collagen III, and TGF-beta1 expression, and Western blot was used to measure collagen protein I expression in tendon sheath fibroblasts after being transfected by antisense TGF-beta1 gene. Reverse transcription polymerase chain reaction displayed that tendon sheath fibroblasts transfected with antisense TGF-beta1 gene showed marked decrease collagen I, collagen III, and TGF-beta1 mRNA expression. Western blot showed that tendon sheath fibroblasts transfected with antisense TGF-beta1 gene showed marked decrease expression of collagen I protein, and there was significant difference compared with the untransfected and empty transfected groups (P<.01). Tendon sheath fibroblasts can transfect with antisense TGF-beta1 gene successfully and can decrease production of collagen I, collagen III, and TGF-beta1, which were factors of tendon adhere formation.