The detection of Gper1 as an important gene promoting jawbone regeneration in the context of estrogen deficiency.

ABSTRACT

Numerous studies have demonstrated that estrogen deficiency inhibit the proliferation and differentiation of pre-osteoblasts in skeleton by affecting osteogenic signaling, lead to decreased bone mass and impaired regeneration. To explore the mechanisms maintaining bone regeneration under estrogen deficiency, we randomly selected 1102 clinical cases, in which female patients aged between 18 and 75 have underwent tooth extraction in Stomatological Hospital of Tongji University, there is little difference in the healing effect of extraction defects, suggesting that to some extent, the regeneration of jawbone is insensitive to the decreased estrogen level. To illuminate the mechanisms promoting jawbone regeneration under estrogen deficiency, a tooth extraction defect model was established in the maxilla of female rats who underwent ovariectomy (OVX) or sham surgery, and jawbone marrow stromal cells (BMSCs) were isolated for single-cell sequencing. Further quantitative PCR, RNA interference, alizarin red staining, immunohistochemistry and western blotting experiments demonstrated that in the context of ovariectomy, maxillary defects promoted G protein-coupled estrogen receptor 1 (Gper1) expression, stimulate downstream cAMP/PKA/pCREB signaling, and facilitate cell proliferation, and thus provided sufficient progenitors for osteogenesis and enhanced the regeneration capacity of the jawbone. Correspondingly, the heterozygous deletion of the Gper1 gene attenuated the phosphorylation of CREB, led to decreased cell proliferation, and impaired the restoration of maxillary defects. This study demonstrates the importance of Gper1 in maintaining jawbone regeneration, especially in the context of estrogen deficiency.