Assistant Professor University of Pennsylvania University of Pennsylvania, Pennsylvania, United States
Abstract: Degenerative joint disease (DJD) of the temporomandibular joint (TMJ) is a debilitating musculoskeletal disorder characterized by morphological and functional abnormalities of the TMJ, which poses a significant challenge in treatment due to the complex nature of the joint and the limited understanding of its underlying causes. Despite its high prevalence, there is currently a lack of effective long-term treatments targeting the root cause of this disease. Therefore, a new therapeutic approach through identifying and activating endogenous mandibular stem/progenitor cell populations is urgently needed for cartilage tissue regeneration. In this study, a cutting-edge single cell (sc) RNA-seq analysis was performed to show a unique in vivo chondroprogenitor cell (CPC) population in mandibular condyle and elucidate their role to contribute to whole mandibular, but not femoral, bone turnover by a Gli1Cre;Ai9 lineage tracing model. Interestingly, computational analysis indicate that mandibular CPCs can directly give rise to osteoblasts, which is similar as neonatal limb CPCs, but not CPCs from adult femoral condyle, indicating a unique Gli1+ CPC population maintains mandibular bone homeostasis. In vitro characterization of Gli1+ CPCs showed that mandibular CPCs have the higher proliferation and multi-lineage differentiation capacities than femoral CPCs, in which EGFR and downstream mTOR signaling is highly activated to maintain stemness of mandibular CPCs. By using a mandibular defect animal model in Gli1Cre;Ai9 reporter mice, our results indicate that Gli1+ CPCs significantly contribute to bone tissue regeneration to maintain mandibular bone homeostasis. Taken together, our findings reveal a unique endogenous chondrocyte progenitor population in mandibular condyle that maintains mandibular bone homeostasis and provides a new therapeutic avenue for regenerative medicine in the temporomandibular joint.
Funding Source: This work was supported in part by NIH/NIDCR-R21DE033128 and NIH/NCI-R01CA288366 to Dr. Chider Chen.
