Smith Margaret M, Melrose James
Raymond Purves Bone and Joint Research Laboratories, Kolling Institute, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, Sydney, NSW 2065, Australia.
Arthropharm Australia Pharmaceuticals Pty Ltd., Bondi Junction, Sydney, NSW 2022, Australia.
Int J Mol Sci. 2025 Sep 19;26(18):9182. doi: 10.3390/ijms26189182.
This review covers the roles of cartilage oligomeric matrix protein (COMP), an established biomarker of cartilage breakdown in pathological tissues in osteoarthritis, and in emerging areas in extracellular matrix and vascular remodeling associated with trauma, fibrosis and cancer. COMP is produced by chondrocytes, tenocytes, myofibroblasts, and in some specialized tissue contexts, endothelial and vascular smooth muscle cells. COMP expression by tendon and cartilage cells is sensitive to weight bearing and tensional mechanical stimulation. Vascular smooth muscle cells are sensitive to shear forces which regulate COMP expression in vascular tissues in atherosclerosis and in carotid stenosis. COMP is a multivalent bridging molecule that stabilizes tissues. It facilitates the signaling of TGF-β and BMP-2 in chondrogenesis, osteogenesis, tissue fibrosis, vascular and ECM remodeling and tumor development by providing a multimeric environment through which growth factor binding and receptor activation can occur. Engineered COMP proteins have been used as molecular templates in the development of chimeric therapeutic proteins of potential application in repair biology. Tie2 (Angiopoietin-1 receptor, Tyrosine-protein kinase receptor TEK), when activated by an engineered COMP-inspired angiopoietin-2 pentamer, is a potent angiogenic molecule of obvious application in wound healing. COMP's multifunctional properties show it is much more than a biomolecular marker protein through its ability to participate in many biological processes. Further studies are warranted to fully explore the biology of this fascinating molecule, particularly in the wound repair processes.
本综述涵盖了软骨寡聚基质蛋白(COMP)的作用,COMP是骨关节炎病理组织中软骨破坏的既定生物标志物,在与创伤、纤维化和癌症相关的细胞外基质和血管重塑等新兴领域也有涉及。COMP由软骨细胞、腱细胞、肌成纤维细胞产生,在某些特殊组织环境中,还由内皮细胞和血管平滑肌细胞产生。肌腱和软骨细胞中的COMP表达对负重和拉伸机械刺激敏感。血管平滑肌细胞对剪切力敏感,剪切力可调节动脉粥样硬化和颈动脉狭窄时血管组织中COMP的表达。COMP是一种多价桥接分子,可稳定组织。它通过提供一个多聚体环境促进转化生长因子-β(TGF-β)和骨形态发生蛋白-2(BMP-2)在软骨形成、骨形成、组织纤维化、血管和细胞外基质重塑以及肿瘤发展中的信号传导,生长因子结合和受体激活可在该环境中发生。工程化的COMP蛋白已被用作分子模板,用于开发在修复生物学中具有潜在应用价值的嵌合治疗蛋白。当被一种受工程化COMP启发的血管生成素-2五聚体激活时,Tie2(血管生成素-1受体,酪氨酸蛋白激酶受体TEK)是一种在伤口愈合中具有明显应用价值的强效血管生成分子。COMP的多功能特性表明,它通过参与许多生物过程,远不止是一种生物分子标记蛋白。有必要进行进一步研究,以充分探索这种迷人分子的生物学特性,特别是在伤口修复过程中的特性。