Bone sialoprotein (gene: Ibsp; 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 Ibsp in mice (Ibsp^−/−) 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 (Ibsp^KAE/KAE) mice and OCCM.30 murine (Ibsp^KAE) cementoblasts. The RGD domain was not critical for acellular or cellular cementum formation in Ibsp^KAE/KAE mice. However, PDL volume and thickness were increased, and significantly more tartrate-resistant acid phosphatase–positive osteoclasts were found on alveolar bone surfaces of Ibsp^KAE/KAE 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：Ibsp；蛋白质：BSP）是一种存在于骨、牙骨质和牙本质中的多功能细胞外基质蛋白。越来越多的证据支持 BSP 通过进化上保守的功能域（包括与细胞外基质-细胞信号传导有关的 C 端整合素结合 Arg-Gly-Asp (RGD) 域）作为矿化组织形成的关键调节因子。小鼠中Ibsp的消融( Ibsp ^−/− ) 会导致骨生长和矿化受损以及破骨细胞生成缺陷，对颅面区域的影响包括脱细胞牙骨质形成减少、牙周韧带 (PDL) 脱离、牙槽骨矿化不足和严重牙周病分解。我们假设 BSP-RGD 在牙骨质和牙槽骨的形成和矿化以及牙周功能中发挥重要作用。通过在 ( Ibsp ^KAE/KAE ) 小鼠和 OCCM.30 小鼠 ( Ibsp ^KAE ) 成牙骨质细胞中用无功能的 Lys-Ala-Glu (KAE) 序列替换 RGD 基序来测试这一假设。RGD 结构域对于Ibsp ^KAE/KAE小鼠的脱细胞或细胞牙骨质形成并不重要。然而，与野生型小鼠相比，Ibsp ^KAE/KAE小鼠的 PDL 体积和厚度增加，并且在牙槽骨表面发现了显着更多的抗酒石酸盐酸性磷酸酶阳性破骨细胞。天狼星红染色、二次谐波生成成像、动态机械分析和阿孢菌素蛋白聚糖定位减少表明 PDL 组织被破坏。体外研究表明 RGD 在细胞迁移、粘附和矿化中发挥作用，这一点通过小骨植入模型得到了证实，其中缺乏 BSP-RGD 的细胞与对照相比显示出明显的缺陷。总的来说，BSP-RGD 结构域与牙周发育有关，尽管体外研究表明变化的规模和范围表明其他因素可能部分补偿并降低体内缺乏 BSP-RGD 的小鼠表型严重程度。