骨性关节炎（OA）是导致关节疼痛和残障的主要疾病，已严重危害人类健康。WNT/β-catenin通路介导的软骨退变和软骨下骨重塑在OA发病过程中至关重要，但其具体机制不明。TRIB2是一个假性激酶，可与转录因子结合调控靶基因活性，被证实是介导WNT/β-catenin通路的关键因子。研究表明，TRIB2能促进胚胎干细胞成骨分化，抑制脂肪前体细胞成脂分化。大量研究发现TRIB2下调C/EBPα的表达，而C/EBPα与破骨分化关系密切。我们前期研究发现，TRIB2抑制软骨细胞退变，调控破骨细胞形成。鉴于TRIB2与WNT/β-catenin通路的密切关系，我们推测TRIB2可能参与WNT/β-catenin通路调控OA的发病过程。本项目拟在细胞与动物水平对其相互作用和机制进行研究，并初步探讨通过调节TRIB2活性缓解OA的可行性，以期为OA防治提供新的理论和实践依据。

Osteoarthritis, the major disease that can cause joint pain and disability, has seriously endangered human health. Cartilage degeneration and subchondral bone remodeling mediated by the WNT/β-catenin pathway play a crucial role in the pathogenesis of osteoarthritis, but the specific mechanism remains to be studied. TRIB2 is a pseudokinase that can bind to transcription factors to regulate target gene' s activity, which has been shown as a key factor in mediating the WNT/β-catenin pathway. Studies have demonstrated that TRIB2 can promote the osteogenic differentiation of embryonic stem cells and inhibit the adipogenic differentiation of adipose precursor cells. Accumulated studies have also found that TRIB2 down-regulates the expression of C/EBPα, while C/EBPα is closely related to osteoclast differentiation. Our previous study found that TRIB2 inhibits chondrocyte degeneration and regulates osteoclast formation. Given the fact that the high consistency was shown between TRIB2 and WNT/β-catenin pathway in cartilage degeneration and subchondral bone remodeling in osteoarthritis, we speculate that TRIB2 was involved in WNT/β-catenin pathway-mediated the progression of osteoarthritis disease. This purpose of this project is to investigate the function and mechanism of TRIB2 in the progression of osteoarthritis disease mediated by WNT/β-catenin signal at the cellular and animal levels, and to explore the feasibility of alleviating the progross of osteoarthritis by regulating TRIB2 activity, thus providing novel theoretical and practical evidence for osteoarthritis prevention and treatment.