Emerging roles of exosomes in oral diseases progression

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.

Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny

Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation.The initiation of Hertwig’s epithelial root sheath(HERS)induces odontoblast differentiation and the subsequent radicular dentin deposition.Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells(DMSCs).Disruptions in these pathways lead to defects in root development,such as shortened roots and furcation abnormalities.Advances in dental stem cells,biomaterials,and bioprinting show immense promise for bioengineered tooth root regeneration.However,replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field.Ongoing research focusing on the mechanisms of root development,advanced biomaterials,and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root.This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.

BMP-IHH-mediated interplay between mesenchymal stem cells and osteoclasts supports calvarial bone homeostasis and repair

Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells(MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein(BMP) signalling and depend on BMP-mediated Indian hedgehog(IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand(RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog(Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMPmediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies

The past decade has seen significant advances in our understanding of Hedgehog(HH)signaling pathway in various biological events.HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium.HH signaling pathway has important functions in embryonic development and tissue homeostasis.It plays a central role in the regulation of the proliferation and differentiation of adult stem cells.Importantly,it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence,malignant progression,poor prognosis and even increased mortality.Understanding the integrative nature of HH signaling pathway has opened up the potential for new therapeutic targets for cancer.A variety of drugs have been developed,including small molecule inhibitors,natural compounds,and long non-coding RNA(LncRNA),some of which are approved for clinical use.This review outlines recent discoveries of HH signaling in tissue homeostasis and cancer and discusses how these advances are paving the way for the development of new biologically based therapies for cancer.Furthermore,we address status quo and limitations of targeted therapies of HH signaling pathway.Insights from this review will help readers understand the function of HH signaling in homeostasis and cancer,as well as opportunities and challenges of therapeutic targets for cancer.