The study for the pathogenesis and treatment of degenerative osteoarthritis: the role of transforming growth factor-b1 (TGF-b1) from bench to bedside

• Main Authors: Shu-Jui Kuo, 郭書瑞
• Other Authors: 湯智昕
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/q3g5cy

博士 === 中國醫藥大學 === 臨床醫學研究所博士班 === 106 === Osteoarthritis (OA) is a highly prevalent disease. Treatmentscomprise intra-articular injection with hyaluronic acid and platelet rich plasma for not severely deformed and total knee arthroplasty (TKA) for severely deformed knees. Despite the high satisfactory rates, periprosthetic joint infection and periprosthetic fracture after TKA are devastating and can lead to mortality. Joint-preserving treatment for degenerative osteoarthritis is the ultimate goal. As for the patients who are inevitable for the arthroplastic surgeries, accuracy and the avoidance of invasiveness are the main issues. Transforming growth factor-b1 (TGF-b1) is an anti-inflammatory cytokine. TGF-b1 not only plays a pivotal role in the pathogenesis of osteoarthritis but also correlates with the severity of surgically induced inflammation. We thus tried to investigate the comprehensive functions of TGF-b1 from the basic to the clinical points of view. The interactions between synovial tissues and the OA-related cytokines actively participate in OA pathogenesis. TGF-b1 has been known to exert the fibrogenic effects on the synovial cells and exert the anti-inflammatory effects on various cell types. However, the anti-inflammatory effects of TGF-b1 on the synovial cells have not been discussed. Heme oxygenase 1 (HO-1) is an inducible anti-inflammatory enzyme. Despite the similar anti-inflammatory profile and their involvement in OA pathogenesis, no studies have explored the association between TGF-1 and HO-1.We showed that TGF-b1 stimulated the expression of HO-1 via activating the PLC-g/PKC-a pathway and suppressing the downstream expression of miRNA-519b. These results may shed light on the pathogenesis and treatment of OA. TGF-b1 also reflects the severity of surgically-induced inflammation. We thus hypothesize that in the TKA surgeries, the milder the extent of bone marrow violation, the lower the postoperative serum TGF-b1 level. We showed that the patients receiving navigation TKAs will have milder postoperative increment of serum inflammatory markers 24 and 72 hours after TKAs, including IL-6, IL-10, TNF-a. The postoperative level of TGF-b1 after navigation TKA was even lower than the preoperative baseline .The concentration of IL-10 in hemovac drainage is also lower after navigation technique. All the inflammatory markers are predictive of major mobility and mortality for patients undergoing lower limb surgeries. Based upon our results, we suggest that the violation of bone marrow during TKA surgeries should be minimized. I would like to incorporate the two major domains of my future work under the linkage of TGF-b1. On the one hand, I try to unravel the pathogensis of OA in order to invent the novel joint-preserving therapy for OA. On the other hand, I would like to refine the existing arthroplastic surgeries to minimize the invasiveness. I hope that my endeavor would make more patients free from the threat of degenerative osteoarthritis and lead a happy life.