chemerin信号通路在骨质疏松症中的作用

Biological effects of chemerin signaling on osteoporosis

chemerin蛋白是一种分泌性的脂肪因子,其生理或病理功能的发挥要求与胞膜上CMKLR1、GPR1或CCRL2三种受体之一相结合,进而激发不同的下游分子事件或静默chemerin信号。chemerin/CMKLR1信号通路在免疫、脂肪生成、能量代谢以及维持骨量等生理进程中发挥作用。由于GPR1与CMKLR1在结构上具有较高的相似度,chemerin/GPR1信号通路也被证明具有类似的功能,目前对这两条信号通路的上下游分子调控机制也有一定的了解。但是,体外实验中chemerin结合CCRL2后,并未出现可检测到的下游信号激活。在骨质疏松的研究领域,对chemerin信号的研究主要集中于与受体CMKLR1结合后的分子事件及其调控。chemerin/CMKLR1信号通路可促进骨髓间充质干细胞(BMSC)成脂分化,抑制其成骨分化,并刺激造血干细胞(HSC)破骨分化,直接影响骨重塑过程,进而引起骨质疏松。干预该通路不仅可以从调控BMSC分化方向的角度刺激新骨形成,还可抑制非依赖成骨细胞的破骨细胞生成过程,减少骨吸收,因而具有治疗骨质疏松的潜力。

Chemerin is a secreted adipokine plays multiple physiological or pathological functions through binding three of its cognitive receptors:CMKLR1, GPR1 or CCRL2, so that to stimulate downstream molecular events or silence chemerin signaling. Chemerin/CMKLR1 signaling was involved in immunity, adipogenesis, energy metabolism and bone mass maintenance. Due to the fact that there was a high structural similarity between GPR1 and CMKLR1,chemerin/ GPR1 signaling had similar functionality in such progresses, and to date, we already had some information about upstream and downstream molecular regulation of both signaling pathways. However, in vitro studies showed no detectable downstream signaling with binding of chemerin and CCRL2. Researches on osteoporosis mainly focused on molecular events and regulation of CMKLR1 signaling with binding of chemerin. Chemerin/CMKLR1 signaling promoted adipogenesis and inhibited osteogenesis of bone mesenchymal stem cells (BMSC), and stimulated osteoclastogenesis of hematopoietic stem cells (HSC), therefore influence bone remodeling and induce osteoporosis. Interference on this signaling could modulate differentiation of BMSC to increase bone formation and inhibit the osteoblast-independent induction of osteoclastogenesis to decrease bone resorption, thus to have potential in osteoporosis treatment.