Exogenous bone sialoprotein improves extraction socket healing in Ibsp knockout and wild-type mice

Abstract

Bone sialoprotein (Ibsp/BSP) is a bone-associated extracellular matrix protein. Ibsp knockout (Ibsp^−/−) mice exhibit defective alveolar bone formation, mineralization, and healing. We hypothesized BSP would rescue defective alveolar bone healing in a molar extraction model in Ibsp^−/− mice. Collagen gel with or without native rat BSP (nBSP) or recombinant rat BSP (rBSP) was delivered to sockets after first maxillary molar extraction in Ibsp^−/− and wild-type (WT) mice. Tissues were harvested 0, 1, 2, 7, and 14 days post-procedure (dpp) and analyzed by micro-computed tomography, histology, and immunohistochemistry (IHC). Histology and IHC demonstrated that collagen and BSP were retained within sockets. At 14 dpp, both bone volume fraction (BV/TV) and bone mineral density (BMD) were increased by both nBSP (over 50 %) and rBSP (over 60 %), compared to collagen alone in Ibsp^−/− mice. In WT alveolar bone, BV/TV and BMD were also increased by nBSP (over 30 %) and rBSP (over 60 %) compared to collagen controls. Gene expression analyses revealed few changes from delivery of nBSP, while addition of rBSP resulted in regulation of cell signaling, ECM, mineralization, and osteoblast/osteoclast-associated genes. Exogenous BSP rescued alveolar bone healing defects in Ibsp^−/− mice and enhanced bone healing in WT mice. Despite both forms of BSP improving bone healing, the substantial differences in how they regulate gene expression suggests that exogenous BSP acts in a complex, multifunctional manner to promote bone healing. These results support BSP as a novel approach to improve the quantity and quality of new bone in socket healing.