Laboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Biosciences Division, College of Dentistry, The Ohio State University, Columbus, OH, USA.
J Dent Res. 2022 Sep;101(10):1238-1247. doi: 10.1177/00220345221100794. Epub 2022 Jun 9.
Bone sialoprotein (gene: ; protein: BSP) is a multifunctional extracellular matrix protein present in bone, cementum, and dentin. Accumulating evidence supports BSP as a key regulator of mineralized tissue formation via evolutionarily conserved functional domains, including a C-terminal integrin-binding Arg-Gly-Asp (RGD) domain implicated in extracellular matrix-cell signaling. Ablation of in mice () results in impaired bone growth and mineralization and defective osteoclastogenesis, with effects in the craniofacial region including reduced acellular cementum formation, detachment of the periodontal ligament (PDL), alveolar bone hypomineralization, and severe periodontal breakdown. We hypothesized that BSP-RGD plays an important role in cementum and alveolar bone formation and mineralization, as well as periodontal function. This hypothesis was tested by replacing the RGD motif with a nonfunctional Lys-Ala-Glu (KAE) sequence in () mice and OCCM.30 murine () cementoblasts. The RGD domain was not critical for acellular or cellular cementum formation in mice. However, PDL volume and thickness were increased, and significantly more tartrate-resistant acid phosphatase-positive osteoclasts were found on alveolar bone surfaces of mice versus wild type mice. PDL organization was disrupted as indicated by picrosirius red stain, second harmonic generation imaging, dynamic mechanical analysis, and decreased asporin proteoglycan localization. In vitro studies implicated RGD functions in cell migration, adhesion, and mineralization, and this was confirmed by an ossicle implant model where cells lacking BSP-RGD showed substantial defects as compared with controls. In total, the BSP-RGD domain is implicated in periodontal development, though the scale and scope of changes indicated by in vitro studies indicate that other factors may partially compensate for and reduce the phenotypic severity of mice lacking BSP-RGD in vivo.
骨唾液蛋白（基因：；蛋白质：BSP）是一种多功能细胞外基质蛋白，存在于骨、牙骨质和牙本质中。越来越多的证据表明，BSP 通过进化保守的功能域（包括一个 C 端整合素结合 Arg-Gly-Asp（RGD）结构域，该结构域与细胞外基质-细胞信号有关）作为矿化组织形成的关键调节剂。在小鼠中敲除（）导致骨生长和矿化受损，破骨细胞生成缺陷，颅面区域的影响包括无细胞牙骨质形成减少、牙周韧带（PDL）分离、牙槽骨矿化不足和严重牙周破坏。我们假设 BSP-RGD 在牙骨质和牙槽骨形成和矿化以及牙周功能中发挥重要作用。通过在（）小鼠和 OCCM.30 鼠（）成牙骨质细胞中用非功能 Lys-Ala-Glu（KAE）序列替换 RGD 基序来检验这一假设。RGD 结构域对于无细胞或细胞牙骨质的形成不是必需的，但在（）小鼠中，PDL 体积和厚度增加，牙槽骨表面上发现的抗酒石酸酸性磷酸酶阳性破骨细胞明显多于野生型小鼠。牙周组织排列紊乱，如苦味酸红染色、二次谐波成像、动态力学分析和减少的天冬氨酸蛋白聚糖定位所示。体外研究表明 RGD 功能在细胞迁移、粘附和矿化中起作用，这通过骨植入模型得到证实，在该模型中，缺乏 BSP-RGD 的细胞与对照相比表现出明显的缺陷。总的来说，BSP-RGD 结构域与牙周发育有关，尽管体外研究表明的变化规模和范围表明，其他因素可能部分补偿并减轻体内缺乏 BSP-RGD 的小鼠的表型严重程度。
