HtrA1 is upregulated during RANKL-induced osteoclastogenesis, and negatively regulates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK and p38 phosphorylation

Xinghuo Wu; Shek Man Chim; Vincent Kuek; Bay Sie Lim; Siu To Chow; Jinmin Zhao; Shuhua Yang; Vicki Rosen; Jennifer Tickner; Jiake Xu

doi:10.1016/j.febslet.2013.11.022

HtrA1 is upregulated during RANKL-induced osteoclastogenesis, and negatively regulates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK and p38 phosphorylation

FEBS Lett. 2014 Jan 3;588(1):143-50. doi: 10.1016/j.febslet.2013.11.022. Epub 2013 Nov 21.

Authors

Xinghuo Wu¹, Shek Man Chim², Vincent Kuek², Bay Sie Lim², Siu To Chow², Jinmin Zhao³, Shuhua Yang⁴, Vicki Rosen⁵, Jennifer Tickner², Jiake Xu⁶

Affiliations

¹ 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.
² School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
³ Research Centre for Regenerative Medicine, Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China.
⁴ Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
⁵ Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
⁶ 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: [email protected].

PMID: 24269886
DOI: 10.1016/j.febslet.2013.11.022

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.

Keywords: Crosstalk; HTRA1; Osteoblast; Osteoclast; RANKL.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Blotting, Western
Bone Morphogenetic Protein 2 / pharmacology
Cell Differentiation / drug effects
Cell Differentiation / genetics
Cell Line
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases / metabolism*
Female
Gene Expression Profiling
High-Temperature Requirement A Serine Peptidase 1
Male
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 14 / metabolism*
Molecular Sequence Data
Osteoblasts / cytology
Osteoblasts / metabolism*
Osteoclasts / cytology
Osteoclasts / drug effects
Osteoclasts / metabolism*
Osteogenesis / drug effects
Osteogenesis / genetics
Phosphorylation / drug effects
RANK Ligand / genetics
RANK Ligand / metabolism
RANK Ligand / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Serine Endopeptidases / genetics
Serine Endopeptidases / metabolism*
Serine Endopeptidases / pharmacology
Smad Proteins / metabolism*
Up-Regulation / drug effects

Substances

Bone Morphogenetic Protein 2
RANK Ligand
Smad Proteins
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase 14
High-Temperature Requirement A Serine Peptidase 1
HtrA1 protein, mouse
Serine Endopeptidases