TGIF1 Gene Silencing in Tendon-Derived Stem Cells Improves the Tendon-to-Bone Insertion Site Regeneration.

BACKGROUND/AIMS: The slow healing process of tendon-to-bone junctions can be accelerated via implanted tendon-derived stem cells (TDSCs) with silenced transforming growth interacting factor 1 (TGIF1) gene. Tendon-to-bone insertion site is the special form of connective tissues derivatives of common connective progenitors, where TGF-ß plays bidirectional effects (chondrogenic or fibrogenic) through different signaling pathways at different stages. A recent study revealed that TGF-ß directly induces the chondrogenic gene Sox9. However, TGIF1 represses the expression of the cartilage master Sox9 gene and changes its expression rate against the fibrogenesis gene Scleraxis (Scx). METHODS: TGIF1 siRNA was transduced or TGIF1 was over-expressed in tendon-derived stem cells. Following suprapinatus tendon repair, rats were either treated with transduced TDSCs or nontransduced TDSCs. Histologic examination and Western blot were performed in both groups. RESULTS: In this study, the silencing of TGIF1 significantly upregulated the chondrogenic genes and markers. Similarly, TGIF1 inhibited TDSC differentiation into cartilage via interactions with TGF-ß-activated Smad2 and suppressed the phosphorylation of Smad2. The area of fibrocartilage at the tendon-bone interface was significantly increased in the TGIF1 (-) group compared with the control and TGIF1-overexpressing groups in the early stages of the animal model. The interface between the tendon and bone showed a increase of new bone and fibrocartilage in the TGIF1 (-) group at 4 weeks. Fibrovascular scar tissue was observed in the TGIF1-overexpressing group and the fibrin glue only group. Low levels of fibrocartilage and fibrovascular scar tissue were found in the TDSCs group. CONCLUSION: Collectively, this study shows that the tendon-derived stem cell modified with TGIF1 gene silencing has promising effects on tendon-to-bone healing which can be further explored as a therapeutic tool in regenerative medicine.

Separate vertical wiring plus bilateral anchor girdle suturing fixation for the fractures of the inferior pole of the patella.

BACKGROUND: The fixation of inferior pole fractures of the patella (IPFPs) is still a great challenge for surgeons. MATERIALS AND METHODS: We introduced a new fixation method for IPFP fixation, that is, separate vertical wiring plus bilateral anchor girdle suturing fixation (SVW-BSAG). Three finite element models including the anterior tension band wiring (ATBW) model, separate vertical wiring (SVW) model and SVW-BSAG model, were built to evaluate the fixation strength of different fixation methods. A total of 41 consecutive patients with IPFP injury were enrolled in this retrospective study, including 23 patients in the ATBW group and 18 patients in the SVW-BSAG group. The operation time, radiation exposure, full weight-bearing time, Bostman score, extension lag versus contralateral healthy leg, Insall-Salvati ratio, and radiograph outcomes were employed to assess and compare the ATBW group and SVW-BSAG group. RESULTS: The finite element analysis confirmed that the SVW-BSAG fixation method was as reliable as the ATBW fixation method in terms of fixed strength. Through retrospective analysis, we found that there was no significant difference between the SVW-BSAG and ATBW groups in age, sex, BMI, fracture side, fracture type, or follow-up time. There were no significant differences between the two groups in the Insall-Salvati ratio, 6-month Bostman score, and fixation failure. Compared with the ATBW group, the SVW-BSAG group showed advantages in intraoperative radiation exposure, full weight-bearing time, and extension lag versus the contralateral healthy leg. CONCLUSION: The finite element analysis and clinical results showed that SVW-BSAG fixation methods are a reliable and valuable for IPFP treatment.

Facile Synthesis of Hollow MnO2 Nanoparticles for Reactive Oxygen Species Scavenging in Osteoarthritis.

Osteoarthritis (OA) is a progressive degenerative joint disease whose molecular mechanism has not been revealed clearly, and there is still no effective approach to cure OA completely. Recently, reactive oxygen species (ROS) are exposed as an important mediator of OA's inflammatory response, and it has been regarded as a therapeutic target for OA treatment. MnO2 nanoparticles possess good biocompatibility and can act as an artificial nanoenzyme to scavenge ROS in various diseases effectively. In this study, the modified Stöber method was applied to synthesize hollow MnO2 (H-MnO2) and H-MnO2 was modified with NH2-PEG-NH2, which possesses excellent biological stability and biocompatibility. It induced a change in the articular cartilage structure changes in vivo, with the knee tissue staining and micro-CT scanning of the whole knee suggesting that H-MnO2 nanoparticles could effectively remove ROS and significantly relieve the inflammatory response of OA without obvious side effects. This study reveals the therapeutic effects of MnO2-based nanomedicine toward OA, which provides potential alternative therapeutic options for patients with inflammation tissue.