Hardy Eugenio, Fernandez-Patron Carlos
Center of Molecular Immunology, Havana, Cuba.
Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada.
Front Physiol. 2020 Feb 5;11:47. doi: 10.3389/fphys.2020.00047. eCollection 2020.
Bone is a dynamic organ that undergoes constant remodeling, an energetically costly process by which old bone is replaced and localized bone defects are repaired to renew the skeleton over time, thereby maintaining skeletal health. This review provides a general overview of bone's main players (bone lining cells, osteocytes, osteoclasts, reversal cells, and osteoblasts) that participate in bone remodeling. Placing emphasis on the family of extracellular matrix metalloproteinases (MMPs), we describe how: (i) Convergence of multiple protease families (including MMPs and cysteine proteinases) ensures complexity and robustness of the bone remodeling process, (ii) Enzymatic activity of MMPs affects bone physiology at the molecular and cellular levels and (iii) Either overexpression or deficiency/insufficiency of individual MMPs impairs healthy bone remodeling and systemic metabolism. Today, it is generally accepted that proteolytic activity is required for the degradation of bone tissue in osteoarthritis and osteoporosis. However, it is increasingly evident that inactivating mutations in MMP genes can also lead to bone pathology including osteolysis and metabolic abnormalities such as delayed growth. We argue that there remains a need to rethink the role played by proteases in bone physiology and pathology.
骨骼是一个动态器官，会不断进行重塑，这是一个能量消耗高昂的过程，通过该过程，旧骨被替换，局部骨缺损得以修复，从而随着时间推移更新骨骼，进而维持骨骼健康。本综述概述了参与骨重塑的主要细胞（骨衬细胞、骨细胞、破骨细胞、转化细胞和成骨细胞）。重点关注细胞外基质金属蛋白酶（MMPs）家族，我们描述了：（i）多个蛋白酶家族（包括MMPs和半胱氨酸蛋白酶）的汇聚如何确保骨重塑过程的复杂性和稳健性，（ii）MMPs的酶活性如何在分子和细胞水平上影响骨生理，以及（iii）单个MMPs的过表达或缺陷/不足如何损害健康的骨重塑和全身代谢。如今，人们普遍认为蛋白水解活性是骨关节炎和骨质疏松症中骨组织降解所必需的。然而，越来越明显的是，MMP基因的失活突变也会导致包括骨溶解和生长迟缓等代谢异常在内的骨病理。我们认为，仍有必要重新思考蛋白酶在骨生理和病理中的作用。
