Molecular Mechanism Of Bcl6 In Cartilage Development And Joint Diseases

Osteoarthritis(OA)is one of the most common joint diseases affecting human health.Many studies find that the main affected tissue of osteoarthritis is articular cartilage.During the development of osteoarthritis,cartilage gradually becomes thinner and eventually becomes wornning.Cartilage cann't repair by itself,which reduces joint mobility and increases pain.At present,it is still a serious problem to explore how to repair cartilage.B cell lymphoma 6(Bcl6)is a transcription factor that expresses in lymphocytes.It regulates the differentiation and proliferation of lymphocytes.Studies shows that Bcl6 is closely related to inflammation.It can inhibit inflammation,cytokines and chemokines.Bcl6 can inhibit osteoclastogenesis and promote osteogenesis.Bcl6 knockout mice showed finger and clavicle with malformation.After severe mechanical loading of knee joint,Bcl6 had differential expression.But it's no clear how bcl6 affects the function of cartilage.We establish Bcl6 cartilage conditional knockout(CKO)mice.In vitro cell experiments,we found that chondrocytes had poor differentiation in Bcl6 cartilage CKO mice.Moreover,the degradation of chondrocytes increased in Bcl6 cartilage CKO mice.In addition,the proliferation of chondrocytes were not change.These experiments showed that Bcl6 might inhibit the degradation of chondrocytes and promote the differentiation of chondrocytes.In animal experiments,it was proved that Bcl6 can also inhibit chondrocytes degradation and promote chondrocytes differentiation in DMM and CDR models.In luciferase and Co IP experiments,we found that BCL6 and SOX9 can interacte to promote the expression of Col2a1.In general,experiments in vivo and in vitro have proved the function and mechanism of Bcl6 in osteoarthritis and cartilage defect repair.It is clear that Bcl6 is a potential target of osteoarthritis.According to the target of Bcl6,drugs can be designed to treat osteoarthritis and cartilage defect repair.