Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
J Cell Biochem. 2010 Jun 1;110(3):573-80. doi: 10.1002/jcb.22604.
Chondrocytes provide the framework for the developing skeleton and regulate long-bone growth through the activity of the growth plate. Chondrocytes in the articular cartilage, found at the ends of bones in diarthroidial joints, are responsible for maintenance of the tissue through synthesis and degradation of the extracellular matrix. The processes of growth, differentiation, cell death and matrix remodeling are regulated by a network of cell signaling pathways in response to a variety of extracellular stimuli. These stimuli consist of soluble ligands, including growth factors and cytokines, extracellular matrix proteins, and mechanical factors that act in concert to regulate chondrocyte function through a variety of canonical and non-canonical signaling pathways. Key chondrocyte signaling pathways include, but are not limited to, the p38, JNK and ERK MAP kinases, the PI-3 kinase-Akt pathway, the Jak-STAT pathway, Rho GTPases and Wnt-beta-catenin and Smad pathways. Modulation of the activity of any of these pathways has been associated with various pathological states in cartilage. This review focuses on the Rho GTPases, the PI-3 kinase-Akt pathway, and some selected aspects of MAP kinase signaling. Most studies to date have examined these pathways in isolation but it is becoming clear that there is significant cross-talk among the pathways and that the overall effects on chondrocyte function depend on the balance in activity of multiple signaling proteins.
软骨细胞为发育中的骨骼提供框架，并通过生长板的活动调节长骨生长。关节软骨中的软骨细胞位于滑膜关节骨的末端，通过细胞外基质的合成和降解来维持组织的正常功能。生长、分化、细胞死亡和基质重塑的过程受到细胞信号通路网络的调节，以响应各种细胞外刺激。这些刺激物包括可溶性配体，如生长因子和细胞因子、细胞外基质蛋白以及机械因子，它们协同作用，通过多种经典和非经典信号通路来调节软骨细胞的功能。关键的软骨细胞信号通路包括但不限于 p38、JNK 和 ERK MAP 激酶、PI-3 激酶-Akt 通路、Jak-STAT 通路、Rho GTPases 和 Wnt-β-catenin 和 Smad 通路。这些通路中任何一条的活性调节都与软骨中的各种病理状态有关。本文综述了 Rho GTPases、PI-3 激酶-Akt 通路以及 MAP 激酶信号转导的一些方面。迄今为止，大多数研究都单独研究了这些通路，但越来越明显的是，这些通路之间存在着显著的串扰，而对软骨细胞功能的总体影响取决于多种信号蛋白活性的平衡。
