Clarification of the function of TIMP3 in fracture healing and development of new fracture healing drug

单核细胞可分化为破骨细胞（OCs）和树突状细胞（DCs），但其分化机制尚不清楚。我们阐明了BMSCs通过自身分泌的TIMP-3上调单核细胞表面M-CSF受体，促进破骨细胞生成，抑制DC分化，破骨细胞生成过程中OCs自身诱导TIMP-3表达，进一步阻断TACE活性，增强M-CSF受体表面表达。本研究表明，骨髓间充质干细胞抑制TACE介导的M-CSF受体脱落可能会失调单核细胞向OC分化，导致骨吸收和骨重建中的抗炎反应。

Monocytes can give rise to osteoclasts (OCs), and dendritic cells (DCs), but these differentiation mechanism is unclear. We clarified that BMSCs up-modulate M-CSF receptor on monocytes through TIMP-3 elaborated by BMSCs to facilitate osteoclastogenesis and suppress DC differentiation, and that TIMP-3 expression is induced in OCs by themselves during osteoclastogenesis to further block TACE activity and enhance the surface expression of M-CSF receptor. This study demonstrated that the suppression of TACE-mediated shedding of M-CSF receptor by BMSCs may dysregulate monocyte differentiation towards OCs to cause bone resorption and anti-inflammatory response in bone remodeling.