title: A Conditional Knockout Mouse Model Reveals a Critical Role of PKD1 in Osteoblast Differentiation and Bone Development.
abstract: The protein kinase D family of serine/threonine kinases, particularly PKD1, has been implicated in the regulation of a complex array of fundamental biological processes. However, its function and mechanism underlying PKD1-mediated the bone development and osteoblast differentiation are not fully understood. Here we demonstrate that loss of PKD1 function led to impaired bone development and osteoblast differentiation through STAT3 and p38 MAPK signaling using in vitro and in vivo bone-specific conditional PKD1-knockout (PKD1-KO) mice models. These mice developed markedly craniofacial dysplasia, scapula dysplasia, long bone length shortage and body weight decrease compared with wild-type littermates. Moreover, deletion of PKD1 in vivo reduced trabecular development and activity of osteoblast development, confirmed by Micro-CT and histological staining as well as expression of osteoblastic marker (OPN, Runx2 and OSX). Mechanistically, loss of PKD1 mediated the downregulation of osteoblast markers and impaired osteoblast differentiation through STAT3 and p38 MAPK signaling pathways. Taken together, these results demonstrated that PKD1 contributes to the osteoblast differentiation and bone development via elevation of osteoblast markers through activation of STAT3 and p38 MAPK signaling pathways.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Shao
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Wanfu
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Jiabi
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Ruonan
authors.initials: R
authors.lastname: Gu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Lai
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Songyu
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Q Jane
authors.initials: QJ
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Deng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001846:Bone Development; D002454:Cell Differentiation; D002460:Cell Line; D005269:Femur / Q000473:pathology; D017353:Gene Deletion; D053612:Janus Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009929:Organ Size; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050396:TRPP Cation Channels / Q000172:deficiency* / Q000378:metabolism; D055114:X-Ray Microtomography; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053612:Janus Kinases; D050796:STAT3 Transcription Factor; D050396:TRPP Cation Channels; D048051:p38 Mitogen-Activated Protein Kinases