title: TRPV1 deletion impaired fracture healing and inhibited osteoclast and osteoblast differentiation.
abstract: Fracture healing, in which osteoclasts and osteoblasts play important roles, has drawn much clinical attention. Osteoclast deficiency or decreased osteoblast activity will impair fracture healing. TRPV1 is a member of the Ca2+permeable cation channel subfamily, and pharmacological inhibition of TRPV1 prevents ovariectomy-induced bone loss, which makes TRPV1 a potential target for osteoporosis. However, whether long term TRPV1 inhibition or TRPV1 deletion will affect the fracture healing process is unclear. In this study, we found that the wild-type mice showed a well-remodeled fracture callus, whereas TRPV1 knockout mice still had an obvious fracture gap with unresorbed soft-callus 4 weeks post-fracture. The number of osteoclasts was reduced in the TRPV1 knockout fracture callus, and osteoclast formation and resorption activity were also impaired in vitro. TRPV1 deletion decreased the calcium oscillation frequency and peak cytoplasmic concentration in osteoclast precursors, subsequently reducing the expression and nuclear translocation of NFATc1 and downregulating DC-stamp, cathepsin K, and ATP6V. In addition, TRPV1 deletion caused reduced mRNA and protein expression of Runx2 and ALP in bone marrow stromal cells (BMSCs) and reduced calcium deposition in vitro. Our results suggest that TRPV1 deletion impairs fracture healing, and inhibited osteoclastogenesis and osteogenesis.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of digital Stomatology, Beijing, China.
authors.forename: Lin-Hai
authors.initials: LH
authors.lastname: He
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of digital Stomatology, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of digital Stomatology, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of digital Stomatology, Beijing, China.
authors.forename: E
authors.initials: E
authors.lastname: Xiao
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of digital Stomatology, Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Center for Craniofacial Stem Cell Research and Regeneration, Department of Orthodontics, Peking University School and Hospital of Stomatology; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of digital Stomatology, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Hua-Qian
authors.initials: HQ
authors.lastname: Yang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of digital Stomatology, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015519:Bone Density; D002146:Bony Callus / Q000473:pathology; D020013:Calcium Signaling; D002356:Cartilage / Q000473:pathology; D002452:Cell Count; D002454:Cell Differentiation; D015536:Down-Regulation; D017102:Fracture Healing; D017353:Gene Deletion; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D050778:NFATC Transcription Factors; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase