title: HtrA1 is upregulated during RANKL-induced osteoclastogenesis, and negatively regulates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK and p38 phosphorylation.
abstract: Bone remodeling is regulated by secreted factors in the bone microenvironment. However, data regarding osteoclast-derived factors that influence osteoblast differentiation are lacking. Here, we show that HtrA1 is produced as a secreted protein during osteoclastogenesis, and negatively regulates osteoblast differentiation. Exogenous addition of recombinant HtrA1 attenuates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK1/2 and p38 phosphorylation in pre-osteoblasts. Our studies imply a unique mode of crosstalk in which HtrA1 is produced by both osteoclasts and osteoblasts and negatively regulates osteoblast differentiation, suggesting that HtrA1 may mediate the fine tuning of paracrine and autocrine regulations during bone remodeling processes.
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Xinghuo
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Shek Man
authors.initials: SM
authors.lastname: Chim
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Kuek
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Bay Sie
authors.initials: BS
authors.lastname: Lim
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Siu To
authors.initials: ST
authors.lastname: Chow
authors.affiliation: Research Centre for Regenerative Medicine, Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yang
authors.affiliation: Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: Vicki
authors.initials: V
authors.lastname: Rosen
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tickner
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia; Research Centre for Regenerative Medicine, Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China. Electronic address: jiake.xu@uwa.edu.au.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D000074289:High-Temperature Requirement A Serine Peptidase 1; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051785:Smad Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D053245:RANK Ligand; D051785:Smad Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048308:Mitogen-Activated Protein Kinase 14; D000074289:High-Temperature Requirement A Serine Peptidase 1; C492073:HtrA1 protein, mouse; D012697:Serine Endopeptidases
keywords: Crosstalk; HTRA1; Osteoblast; Osteoclast; RANKL