Different Responsiveness of Alveolar Bone and Long Bone to Epithelial‐Mesenchymal Interaction‐Related Factor

Alveolar bone is both morphologically and functionally different from other bones of the axial or peripheral skeleton. Because of its sensitive nature to external stimuli including mechanical stress, bone loss stimuli, and medication-related osteonecrosis of the jaw, alveolar bone rendering is seen as an important factor in various dental surgical processes. Although multiple studies have validated the response of long bone to various factors, how alveolar bone responds to functional stimuli still needs further clarification. To examine the characteristics of bone in vitro, we isolated cells from alveolar, femur, and tibia bone tissue. Although primary cultured mouse alveolar bone-derived cells (mABDCs) and mouse long bone-derived cells (mLBDCs) exhibited similar osteoblastic characteristics, morphology, and proliferation rates, both showed distinct expression of neural crest (NC) and epithelial-mesenchymal interaction (EMI)-related genes. Furthermore, they showed significantly different mineralization rates. RNA sequencing data demonstrated distinct transcriptome profiles of alveolar bone and long bone. Osteogenic, NC-, and EMI-related genes showed distinct expression between mABDCs and mLBDCs. When the gene expression patterns during osteogenic differentiation were analyzed, excluding several osteogenic genes, NC- and EMI-related genes showed different expression patterns. Among EMI-related proteins, BMP4 elevated the expression levels of osteogenic genes, Msx2, Dlx5, and Bmp2 the most, more noticeably in mABDCs than in mLBDCs during osteogenic differentiation. In in vivo models, the BMP4-treated mABDC group showed massive bone formation and maturation as opposed to its counterpart. Bone sialoprotein expression was also validated in calcified tissues. Overall, our data suggest that alveolar bone and long bone have different responsiveness to EMI by distinct gene regulation. In particular, BMP4 has critical bone formation effects on alveolar bone, but not on long bone. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.