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Background/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteoclastogenesis and bone homeostasis. Methods: In the present study, exon 3 in the β-catenin gene (Ctnnb1) allele encoding phosphorylation target serine/threonine residues was flanked by floxP sequences. We generated mice exhibiting conditional β-catenin activation (Ctsk-Cre;Ctnnb1^{flox(exon3)/+}, designated CA-β-catenin) by crossing Ctnnb1^{flox(exon3)/flox(exon3)} mice with osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by micro-computed tomography (micro-CT) and histomorphometry. To further examine osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs) isolated from CA-β-catenin and Control mice in vitro. Osteoclast differentiation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining and reverse transcription-quantitative PCR (RT–qPCR) analysis. Results: Growth retardation and low bone mass were observed in CA-β-catenin mice. Compared to controls, CA-β-catenin mice had significantly reduced trabecular bone numbers under growth plates as well as thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were observed on the surfaces of trabecular bones and cortical bones in the CA-β-catenin mice; consistent results were observed in vitro. In the CA-β-catenin group, excessive numbers of osteoclasts were induced from BMMs, accompanied by the increased expression of osteoclast-associated marker genes. Conclusion: These results indicated that the constitutive activation of β-catenin in osteoclasts promotes osteoclast formation, resulting in bone loss.

Enamel is the hardest tissue with the highest degree of mineralization protecting the dental pulp from injury in vertebrates. The ameloblasts differentiated from ectoderm-derived epithelial cells are a single cell layer and are important for the enamel formation and mineralization. Wnt/β-catenin signaling has been proven to exert an important role in the mineralization of bone, dentin and cementum. Little was known about the regulatory mechanism of Wnt/β-catenin signaling pathway in ameloblasts during amelogenesis, especially in the mineralization of enamel. To investigate the role of β-catenin in ameloblasts, we established Amelx-Cre; β-catenin (CA-β-catenin) mice, which could constitutive activate β-catenin in ameloblasts. It showed the delayed mineralization and eventual hypomineralization in the incisor enamel of CA-β-catenin mice. Meanwhile, the amelogenesis-related proteinases Mmp20 and Klk4 were decreased in the incisors of CA-β-catenin mice. These data indicated that β-catenin plays an essential role in differentiation and function of ameloblasts during amelogenesis.

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Epithelial rests of Malassez (ERM), the only odontogenic epithelial structures in periodontal tissue, are proposed to correlate with root resorption, but the detailed mechanism remains unclear. Osteoprotegerin (OPG), the main inhibitor of osteoclastogenesis, plays a pivotal role in inhibiting root resorption, and ERM cells express OPG mRNA in vitro. Thus, in this study, we aimed to clarify OPG expression in ERM in vivo and to explore the role of OPG in ERM to determine whether ERM are associated with root resorption via OPG. We established Opg-knockout (Opg-KO) mice and detected the OPG expression in ERM by immunohistochemical staining in 4-, 6-, 10-, 26- and 52-week-old mice. The ERM of wild-type (WT) mice and Opg-KO mice were evaluated histologically at 4, 10 and 26 weeks of age. Orthodontic root resorption models were established, maxillae were collected after 4 weeks, and ERM were analysed by histomorphometric analysis. In our study, OPG displayed sustained expression in ERM, and OPG deficiency caused the destruction of ERM, characterized by irregular morphology and reduced numbers. Moreover, after orthodontic treatment, the loss of OPG severely damaged ERM, aggravating root resorption. Together, our results demonstrated that ERM expressed the OPG protein in vivo and that OPG deficiency resulted in morphological and quantitative damage to ERM. Furthermore, ERM may be associated with root resorption via OPG, thus helping to explain the mechanism underlying root resorption.