The sensory nerve was recently identified as being involved in regulation of bone mass accrual. We previously discovered that prostaglandin E₂ (PGE2) secreted by osteoblasts could activate sensory nerve EP4 receptor to promote bone formation by inhibiting sympathetic activity. However, the fundamental units of bone formation are active osteoblasts, which originate from mesenchymal stromal/stem cells (MSCs). Here, we found that after sensory denervation, knockout of the EP4 receptor in sensory nerves, or knockout of COX-2 in osteoblasts, could significantly promote adipogenesis and inhibit osteogenesis in adult mice. Furthermore, injection of SW033291 (a small molecule that locally increases the PGE2 level) or propranolol (a beta blocker) significantly promoted osteogenesis and inhibited adipogenesis. This effect of SW033291, but not propranolol, was abolished in conditional EP4-KO mice under normal conditions or in the bone repair process. We conclude that the PGE2/EP4 sensory nerve axis could regulate MSC differentiation in bone marrow of adult mice.

Restoring the normal structure and function of injured tendons is one of the biggest challenges in orthopedics and sports medicine department. The discovery of tendon-derived stem cells (TDSCs) provides a novel perspective to treat tendon injuries, which is expected to be an ideal seed cell to promote tendon repair and regeneration. Because of the lack of specific markers, the identification of tenocytes and TDSCs has not been conclusive in thein vitrostudy of tendons. In addition, the morphology of tendon derived cells is similar, and the comparison and identification of tenocytes and TDSCs are insufficient, which causes some obstacles to thein vitrostudy of tendon. In this review, the characteristics of tenocytes and TDSCs are summarized and compared based on some existing research results (mainly in terms of biomarkers), and a potential marker selection for identification is suggested. It is of profound significance to further explore the mechanism of biomarkersin vivoand to find more specific markers.