Departments of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
J Dent Res. 2021 Nov;100(12):1359-1366. doi: 10.1177/00220345211007447. Epub 2021 Apr 24.
Bone loss caused by trauma, neoplasia, congenital defects, or periodontal disease is a major cause of disability and human suffering. Skeletal progenitor cell-extracellular matrix interactions are critical for bone regeneration. Discoidin domain receptor 2 (DDR2), an understudied collagen receptor, plays an important role in skeletal development. loss-of-function mutations in humans and mice cause severe craniofacial and skeletal defects, including altered cranial shape, dwarfing, reduced trabecular and cortical bone, alveolar bone/periodontal defects, and altered dentition. However, the role of this collagen receptor in craniofacial regeneration has not been examined. To address this, calvarial subcritical-size defects were generated in wild-type (WT) and deficient mice. The complete bridging seen in WT controls at 4 wk postsurgery was not observed in deficient mice even after 12 wk. Quantitation of defect bone area by micro-computed tomography also revealed a 50% reduction in new bone volume in deficient mice. expression during calvarial bone regeneration was measured using knock-in mice. Expression was restricted to periosteal surfaces of uninjured calvarial bone and, after injury, was detected in select regions of the defect site by 3 d postsurgery and expanded during the healing process. The impaired bone healing associated with deficiency may be related to reduced osteoprogenitor or osteoblast cell proliferation and differentiation since knockdown/knockout of in a mesenchymal cell line and primary calvarial osteoblast cultures reduced osteoblast differentiation while overexpression was stimulatory. In conclusion, is required for cranial bone regeneration and may be a novel target for therapy.
创伤、肿瘤、先天缺陷或牙周病引起的骨丢失是导致残疾和人类痛苦的主要原因。骨骼祖细胞-细胞外基质相互作用对于骨再生至关重要。盘状结构域受体 2 (DDR2)，一种研究较少的胶原受体，在骨骼发育中发挥重要作用。人类和小鼠中的功能丧失突变导致严重的颅面和骨骼缺陷，包括颅骨形状改变、矮小、小梁和皮质骨减少、牙槽骨/牙周缺陷以及牙齿改变。然而，这种胶原受体在颅面再生中的作用尚未被研究。为了解决这个问题，在野生型 (WT) 和缺陷型小鼠中生成了颅骨亚临界大小的缺损。在手术后 4 周，WT 对照组中完全桥接，但在缺陷型小鼠中甚至在 12 周后也未观察到。通过微计算机断层扫描对缺陷骨面积的定量也显示缺陷型小鼠的新骨体积减少了 50%。在颅骨骨再生过程中使用 敲入小鼠测量 表达。表达仅限于未受伤颅骨骨的骨膜表面，并且在手术后 3 天在缺陷部位的特定区域检测到，并在愈合过程中扩展。与 缺陷相关的骨愈合受损可能与成骨前体细胞或成骨细胞增殖和分化减少有关，因为在间充质细胞系和原代颅骨成骨细胞培养物中敲低/敲除 减少了成骨细胞分化，而 过表达具有刺激作用。总之， 对于颅骨骨再生是必需的，并且可能是一种新的治疗靶点。
