Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA.
College of Dentistry, University of Iowa, Iowa City, IA, USA.
J Dent Res. 2023 Feb;102(2):187-196. doi: 10.1177/00220345221126716. Epub 2022 Nov 14.
Bone sialoprotein (BSP) is an extracellular matrix (ECM) protein associated with mineralized tissues, particularly bone and cementum. BSP includes functional domains implicated in collagen binding, hydroxyapatite nucleation, and cell signaling, although its function(s) in osteoblast and osteoclast differentiation and function remain incompletely understood. Genetic ablation of BSP in knockout () mice results in developmental bone mineralization and remodeling defects, with alveolar bone more severely affected than the femurs and tibias of the postcranial skeleton. The role of BSP in alveolar bone healing has not been studied. We hypothesized that BSP ablation would cause defective alveolar bone healing. We employed a maxillary first molar extraction socket healing model in 42-d postnatal and wild-type (WT) control mice. Tissues were collected at 0, 7, 14, 21, and 56 d postprocedure (dpp) for analysis by micro-computed tomography (microCT), histology, in situ hybridization (ISH), immunohistochemistry (IHC), and quantitative polymerase chain reaction (qPCR) array. As expected, alveolar bone healing progressed in WT mice with increasing bone volume fraction (BV/TV), bone mineral density (BMD), and tissue mineral density (TMD), transitioning from woven to mature bone from 7 to 56 dpp. messenger RNA (mRNA) and BSP protein were strongly expressed during alveolar bone healing in parallel with other osteogenic markers. Compared to WT, mice exhibited 50% to 70% reduced BV/TV and BMD at all time points, 7% reduced TMD at 21 dpp, abnormally increased and mRNA expression, and persistent presence of woven bone and increased bone marrow in healing sockets. qPCR revealed substantially dysregulated gene expression in alveolar bone of versus WT mice, with significantly disrupted expression of 45% of tested genes in functional groups, including markers for osteoblasts, osteoclasts, mineralization, ECM, cell signaling, and inflammation. We conclude that BSP is a critical and nonredundant factor for alveolar bone healing, and its absence disrupts multiple major pathways involved in appropriate healing.
骨涎蛋白（BSP）是一种细胞外基质（ECM）蛋白，与矿化组织，特别是骨骼和牙骨质有关。BSP 包含与胶原结合、羟基磷灰石成核和细胞信号传导相关的功能域，尽管其在成骨细胞和破骨细胞分化和功能中的作用仍不完全清楚。在 基因敲除（ ）小鼠中，BSP 的遗传缺失导致发育性骨矿化和重塑缺陷，牙槽骨比颅后骨骼的股骨和胫骨受影响更严重。BSP 在牙槽骨愈合中的作用尚未研究。我们假设 BSP 缺失会导致牙槽骨愈合缺陷。我们在 42 天龄的新生和野生型（WT）对照小鼠中使用上颌第一磨牙拔牙窝愈合模型。在程序后 0、7、14、21 和 56 天（dpp）收集组织，通过微计算机断层扫描（microCT）、组织学、原位杂交（ISH）、免疫组织化学（IHC）和定量聚合酶链反应（qPCR）阵列进行分析。正如预期的那样，牙槽骨愈合在 WT 小鼠中进展，骨体积分数（BV/TV）、骨矿物质密度（BMD）和组织矿物质密度（TMD）增加，从 7 天到 56 天从编织骨向成熟骨过渡。 信使 RNA（mRNA）和 BSP 蛋白在牙槽骨愈合过程中与其他成骨标记物平行强烈表达。与 WT 相比， 小鼠在所有时间点的 BV/TV 和 BMD 降低 50%至 70%，21 天的 TMD 降低 7%，异常增加的 和 mRNA 表达，以及愈合窝中持续存在的编织骨和增加的骨髓。qPCR 显示，与 WT 相比， 小鼠的牙槽骨基因表达明显失调，在功能组中测试的 45%的基因表达显著紊乱，包括成骨细胞、破骨细胞、矿化、细胞外基质、细胞信号传导和炎症的标记物。我们得出结论，BSP 是牙槽骨愈合的关键且不可或缺的因素，其缺失会破坏适当愈合中涉及的多个主要途径。
