Faculty of Dentistry, McGill University, Montreal, Quebec, Canada; Shriners Hospital for Children-Canada, Montreal, Quebec H3G 1A6, Canada.
Shriners Hospital for Children-Canada, Montreal, Quebec H3G 1A6, Canada.
Bone. 2018 Dec;117:23-30. doi: 10.1016/j.bone.2018.09.006. Epub 2018 Sep 12.
The major organic component of bone is collagen type I. Osteoclasts are terminally differentiated multinucleated cells of hematopoietic origin that are essential for physiological development of bone and teeth. We examined if osteoclast differentiation from murine bone marrow precursors is affected by collagen type I, or by its degradation products produced by human recombinant cathepsin K. Osteoclasts formation was dose-dependently inhibited in the presence of full length collagen type I or its 30-75 kDa degradation products added to the osteoclast differentiation media for the duration of an experiment. Collagen degradation fragments signaled through SH-2 phosphatases, inhibiting calcium signaling and NFATc1 translocation in osteoclast precursors. Osteoclasts and their precursors expressed a collagen receptor of leukocyte receptor complex family, LAIR-1. Importantly, collagen fragments failed to inhibit osteoclast formation from LAIR-1 deficient murine osteoclast precursors. This study demonstrates that collagen degradation fragments inhibit osteoclast formation acting through LAIR-1, providing a novel mechanism for the physiologically-relevant negative control of osteoclastogenesis.
骨的主要有机成分是 I 型胶原。破骨细胞是终末分化的多倍体细胞，来源于造血系统，对于骨骼和牙齿的生理发育至关重要。我们研究了 I 型胶原或其由人重组组织蛋白酶 K 产生的降解产物是否会影响鼠骨髓前体细胞的破骨细胞分化。在整个实验过程中，向破骨细胞分化培养基中添加全长 I 型胶原或其 30-75 kDa 的降解产物，会使破骨细胞形成呈剂量依赖性抑制。胶原降解片段通过 SH-2 磷酸酶发出信号，抑制破骨细胞前体中的钙信号和 NFATc1 易位。破骨细胞及其前体表达白细胞受体复合物家族的胶原受体 LAIR-1。重要的是，胶原片段无法抑制 LAIR-1 缺陷型鼠破骨细胞前体的破骨细胞形成。本研究表明，胶原降解片段通过 LAIR-1 抑制破骨细胞形成，为破骨细胞生成的生理相关负调控提供了新的机制。
