Bone is a highly vascularized organ that not only plays multiple roles in supporting the body and organs but also endows the microstructure, enabling distinct cell lineages to reciprocally interact. Recent studies have uncovered relevant roles of the bone vasculature in bone patterning, morphogenesis, homeostasis, and pathological bone destruction, including osteoporosis and tumor metastasis. This review provides an overview of current topics in the interactive molecular events between endothelial cells and bone cells during bone ontogeny and discusses the future direction of this research area to find novel ways to treat bone diseases.

Degenerative joint disease of the temporomandibular joints (DJD-TMJ) clinically manifests with symptoms such as orofacial pain, joint sounds and limited jaw movements. Our research group previously reported the functional necessity of a chemokine-chemokine receptor axis of CCL5-CCR5 in osteoclasts. Accumulated studies reported that this axis was involved in the pathogenesis of bone and joint destructive diseases, suggesting CCL5 as a potent biomarker. This study investigated whether or not the serum level of CCL5 can be a biomarker of DJD-TMJ and concomitantly analyzed changes in the serum and urine levels of bone markers to see whether or not changes in the rate of bone metabolism were predisposing. We enrolled 17 female subjects with diagnosed DJD-TMJ and sexually and age-matched 17 controls. The serum CCL5 level in DJD-TMJ subjects was significantly higher than that in the control subjects. Multivariate analyses indicated an association between an augmented CCL5 level and the rate of bone metabolism, especially in relatively young DJD-TMJ subjects without other systemic symptoms. A principal component analysis of serum markers and our pharmacological experiment using a postmenopausal model of ovariectomized rats suggested that an augmented serum CCL5 level specifically reflected DJD-TMJ and that covert changes in the rate of bone metabolism predisposed individuals to DJD-TMJ.

Pregnancy- and lactation-associated osteoporosis (PLO) is receiving increasing attention. During pregnancy and lactation, bone metabolism is dramatically changed to supply minerals to the fetus and infant, which is a major cause of PLO. Weaning of lactation is clinically a primary choice to treat lactation-induced osteoporosis since breastfeeding is a key regulator of the pathophysiology during lactation. However, breastfeeding is beneficial to the physical and mental development of infants. We also discuss the beneficial effects of breastfeeding on the oral and maxillofacial development of infants. Pharmacological treatment of PLO is also discussed. This review also discusses how dynamic regulatory changes in bone metabolism during pregnancy and lactation affect homeostasis of the temporomandibular joint (TMJ) and alveolar bone in mothers, from the perspectives of TMJ diseases and orthodontic treatment.

Chemokine receptor 5 (CCR5)-mediated signals are involved in various biological responses and inflammatory diseases. Recent studies have revealed the roles of this signaling pathway in bone metabolism, metabolic bone diseases, and joint diseases. Through preclinical and clinical studies, our research group has demonstrated that CCR5 signaling is deeply involved in degenerative changes in the temporomandibular joint (TMJ). In this short review, we outline the diverse functions of CCR5 signaling in oral and degenerative TMJ diseases.

Mandibular prognathism (MP) is a type of malocclusion characterized by an imbalance in the anteroposterior position of the upper and lower jaws. The prevalence of MP in Japan is relatively high, suggesting a unique genetic background in the population. Genome-wide analyses identified susceptibility genes responsible for mandibular prognathism in the Japanese population. Identification of the genes associated with malocclusion will pave the way for personalized and precise medicine and contribute to craniofacial biology.