ETS2 overexpression ameliorates cartilage injury in osteoarthritis by the ETS2/miR-155/STAT1/DNMT1 feedback loop pathway.

Osteoarthritis (OA) is the most common irreversible chronic joint dysfunction disease, which is pathologically characterized by disturbance of articular cartilage homeostasis leading to subsequent inflammatory response and cartilage extracellular matrix (ECM) degradation. Increasing evidence has demonstrated the dysregulation of transcription factors play crucial roles in the occurrence and development of osteoarthritis (OA), but the potential functions and mechanism of most transcription factors in OA has not been completely illuminated. In this study, we identified that transcription factor V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) was significantly down-regulated in OA cartilage and IL-1ß-induced OA chondrocytes. Functional experiments in vitro demonstrated that the overexpressed ETS2 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and ECM degradation in IL-1ß-induced OA chondrocytes, whereas the knockdown of ETS2 led to the opposite effects. Further in vivo studies have shown that up-regulated ETS2 dramatically ameliorates cartilage injury in DMM-induced OA mice. Mechanical studies have disclosed that DNMT1-mediated downregulation of ETS2 dramatically promotes STAT1 by inhibiting miR-155 transcription, and increased STAT1 initiates a feedback loop that may enhance DNMT1-mediated hypermethylation of ETS2 to inhibit ETS2 expression, thus forming a DNMT1/ETS2/miR-155/STAT1 feedback loop that inhibits MAPK signaling pathways and aggravates OA cartilage injury. In all, our results revealed that overexpression of ETS2 markedly ameliorated OA cartilage injury through the ETS2/miR-155/STAT1/DNMT1 feedback loop, providing a new perspective on the pathogenesis and therapeutic strategies for OA.

[Comparative study on reconstruction of anterior cruciate ligaments with allografts and hamstring tendon under arthroscopy].

OBJECTIVE: To evaluate the effect of reconstruction of anterior cruciate ligaments (ACL) with allogeneic tendon or autologous hamstring tendon under arthroscopy. METHODS: Thirty-two cases of ACL injury (3 cases compound with PCL injury) were reviewed. All the patients were divided into two groups randomly. Fifteen cases were reconstructed with hamstring tendon, including 12 male and 3 female with the age ranging from 23 to 61 years. Seventeen cases were reconstructed with allograft, including 11 male and 6 female with the age ranging from 17 to 57 years. The tendons were fixed with absorbable or Ti screws. All patients were recorded symptoms,physical signs and Lysholm Scores two weeks after operation,and functional rehabilitation of knee six months after operation. RESULTS: All cases were followed up from 6 to 8 months. Pain and clinical symptoms disappeared and the function of knee joint was improved in all patients. Five patients of allograft with positive Lachman test result,one with severe graft rejection was found complete absorption of allograft under arthroscopy. No significant differences were seen in Lysholm Score between the two groups,average (88.5 +/- 7.2), (93.2 +/- 8.5) after operation (P > 0.05). CONCLUSION: The effects of reconstruction of cruciate ligaments with allogeneic tendon or autologous hamstring tendon under arthroscopy are more satisfying. But there are more symptoms and obvious individual differences in the earlier stage of rehabilitation. So reconstruction of cruciate ligaments under arthroscopy using autologous hamstring tendon should be performed as far as possible.