Mandibular fractures remain a challenging clinical entity and are commonly associated with injury of the inferior alveolar nerve (IAN). Previous research by our group has identified the mouse skeletal stem cell (mSSC) and demonstrated its role as enactors of bone generation during and during mandibular fracture repair and mandibular distraction osteogenesis, a postnatal regenerative paradigm. While it is known that denervation results in impaired tissue regeneration, the direct effect of denervation on stem cells that enact these processes is unknown. We devised a novel model of mandibular denervation to examine the nerve dependency of the mSSC during mandibular fracture healing. We show that denervation of the inferior alveolar nerve is associated with compromised mandibular bone repair due to quantitative and functional defects in mSSCs. We present mSSC reliance upon paracrine factors secreted by Schwann cells as the underlying mechanism for this finding, with rescue of the denervation phenotype by Schwann-derived growth factors. We also show that mandibular fracture leads to expansion and increased regenerative capacity of the human skeletal stem cells (hSSC). This work may have implications for skeletal tissue engineering and treatment of mandibular defects, which remain a challenging clinical problem. This work may have implications for skeletal tissue engineering and treatment of mandibular defects.