Maxillofacial bone defects are commonly seen in clinical practice.A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches f...Maxillofacial bone defects are commonly seen in clinical practice.A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches for bone regeneration.The fibroblast growth factor(FGF)signalling pathway is critical for the development of maxillofacial bone.Klotho,a type I transmembrane protein,is an important components of FGF receptor complexes.Recent studies have reported the presence of Klotho expression in bone.However,the role of Klotho in cranioskeletal development and repair remains unknown.Here,we use a genetic strategy to report that deletion of Klotho in Osx-positive mesenchymal progenitors leads to a significant reduction in osteogenesis under physiological and pathological conditions.Klotho-deficient mensenchymal progenitors also suppress osteoclastogenesis in vitro and in vivo.Under conditions of inflammation and trauma-induced bone loss,we find that Klotho exerts an inhibitory function on inflammation-induced TNFR signaling by attenuating Rankl expression.More importantly,we show for the first time that Klotho is present in human alveolar bone,with a distinct expression pattern under both normal and pathological conditions.In summary,our results identify the mechanism whereby Klotho expressed in Osx+-mensenchymal progenitors controls osteoblast differentiation and osteoclastogenesis during mandibular alveolar bone formation and repair.Klotho-mediated signaling is an important component of alveolar bone remodeling and regeneration.It may also be a target for future therapeutics.展开更多
基金supported by NSFC grants 81800928,81901040,and 82171001the Young Elite Scientist Sponsorship Program by CAST(No.2020QNRC001 and 2018QNR001)+2 种基金the Sichuan Science and Technology Program(No.2019YJ0054)Research Funding from West China School/Hospital of Stomatology Sichuan University(No.RCDWJS2021-1)State Key Laboratory of Oral Diseases Open Funding Grant SKLOD202114.
文摘Maxillofacial bone defects are commonly seen in clinical practice.A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches for bone regeneration.The fibroblast growth factor(FGF)signalling pathway is critical for the development of maxillofacial bone.Klotho,a type I transmembrane protein,is an important components of FGF receptor complexes.Recent studies have reported the presence of Klotho expression in bone.However,the role of Klotho in cranioskeletal development and repair remains unknown.Here,we use a genetic strategy to report that deletion of Klotho in Osx-positive mesenchymal progenitors leads to a significant reduction in osteogenesis under physiological and pathological conditions.Klotho-deficient mensenchymal progenitors also suppress osteoclastogenesis in vitro and in vivo.Under conditions of inflammation and trauma-induced bone loss,we find that Klotho exerts an inhibitory function on inflammation-induced TNFR signaling by attenuating Rankl expression.More importantly,we show for the first time that Klotho is present in human alveolar bone,with a distinct expression pattern under both normal and pathological conditions.In summary,our results identify the mechanism whereby Klotho expressed in Osx+-mensenchymal progenitors controls osteoblast differentiation and osteoclastogenesis during mandibular alveolar bone formation and repair.Klotho-mediated signaling is an important component of alveolar bone remodeling and regeneration.It may also be a target for future therapeutics.
