Probiotics serve as a novel preventive or therapeutic approach for dental caries owing to their ability to reverse dysbiosis and restore a healthy microbiota. Here, we identified Burkholderia ambifaria AFS098024 as a probiotic candidate isolated from plants. The safety of B. ambifaria was evaluated by hemolytic activity, D-lactic acid production and antibiotic susceptibility. In vitro biofilm model derived from the saliva of caries-free and caries-active donors and in vivo rat caries model were used to assess the efficacy of B. ambifaria in caries prevention and treatment. B. ambifaria was safe as a probiotic candidate and it could integrate with in vitro biofilm model. It significantly reduced the biomass and lactate production of biofilms from caries-active donors and disrupted biofilm structures. B. ambifaria effectively reduced the severity of carious lesions in rat molars, regardless of the inoculation sequence. Molars pretreated or treated with B. ambifaria demonstrated notably higher enamel volumes. Additionally, colonization of rat molars by B. ambifaria persisted for 6 weeks. The B. ambifaria strain used in this study holds promise as a probiotic for inhibiting dental caries, both in vitro and in vivo.

Bone-related diseases represent a significant global health challenge characterized by compromised bone mass and dysregulated skeletal metabolism. Mesenchymal stem cells (MSCs) are indispensable for maintaining bone homeostasis and facilitating tissue repair. However, their regenerative capacity is severely compromised in pathological microenvironments. Recent evidence highlights that MSC functionality is intrinsically governed by a sophisticated mitochondrial quality control (MQC) network, primarily encompassing mitochondrial biogenesis, dynamics, and mitophagy. While the importance of MQC is recognized, a comprehensive understanding of how its specific dysregulation in MSCs drives major bone disorders remains limited. This review systematically summarizes how MQC dysregulation in MSCs contributes to the exacerbation of major bone disorders, including osteoporosis, osteonecrosis of the femoral head, osteoarthritis, intervertebral disc degeneration, and periodontitis. Furthermore, as mitochondrial restoration emerges as a critical factor for therapeutic outcomes, this review evaluates promising approaches, ranging from small molecule drugs to biomaterials and cell-based therapies, highlighting the underlying pathways by which they modulate MQC networks to rescue MSC function. We aim to provide mechanistic insights into the role of MSC-related MQC in bone health and explore potential therapeutic prospects for ameliorating bone diseases by restoring MQC homeostasis in MSCs.

Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects on account of inappropriate tissue metabolism and cellular differentiation. The coordinated activity of differentiation and viability in bone cells is indispensable for bone metabolism. Recent research demonstrates mesenchymal progenitors are responsive to PTH1R signaling for osteogenic differentiation, whereas the effect of PTH1R on cellular survival remains incompletely understood. Here, we report that mice with deletion of PTH1R in Prx1-positive mesenchymal cells (Prx1Cre;PTH1R^fl/fl) exhibit decreased alveolar bone mass due in part to apoptotic response activation. The exploration of oral bone-derived mesenchymal stem cells (OMSCs) with PTH1R deficiency suggests PTH1R signaling modulates OMSCs’ apoptosis by interfering mitochondrial function and morphology. The underlying molecular mechanisms are studied by transcriptome sequencing analysis, finding that inositol trisphosphate receptor-3 (IP3R-3), an endoplasmic reticulum calcium channel protein, serves as a modulator of pro-apoptosis in OMSCs. Furthermore, we find PTH1R and its downstream protein kinase A (PKA) pathway dampen IP3R-3’s expression. Of note, OMSCs with IP3R-3 overexpression recapitulate the PTH1R-deletion phenotypes, while IP3R-3 silence rescues mitochondrial dysfunction. Altogether, our study uncovers the anti-apoptotic function of PTH1R signaling in OMSCs and proves that excess apoptosis partly contributes to a weakening potential of osteogenic differentiation and aberrant mandibular development.