RRC ID 45219
Author Asai N, Ohkawara B, Ito M, Masuda A, Ishiguro N, Ohno K.
Title LRP4 induces extracellular matrix productions and facilitates chondrocyte differentiation.
Journal Biochem Biophys Res Commun
Abstract Endochondral ossification is an essential step for skeletal development, which requires chondrocyte differentiation in growth cartilage. The low-density lipoprotein receptor-related protein 4 (LRP4), a member of LDLR family, is an inhibitor for Wnt signaling, but its roles in chondrocyte differentiation remain to be investigated. Here we found by laser capture microdissection that LRP4 expression was induced during chondrocyte differentiation in growth plate. In order to address the roles, we overexpressed recombinant human LRP4 or knocked down endogenous LRP4 by lentivirus in mouse ATDC5 chondrocyte cells. We found that LRP4 induced gene expressions of extracellular matrix proteins of type II collagen (Col2a1), aggrecan (Acan), and type X collagen (Col10a1), as well as production of total proteoglycans in ATDC5 cells, whereas LRP4 knockdown had opposite effects. Interestingly, LRP4-knockdown reduced mRNA expression of Sox9, a master regulator for chondrogenesis, as well as Dkk1, an extracellular Wnt inhibitor. Analysis of Wnt signaling revealed that LRP4 blocked the Wnt/β-catenin signaling activity in ATDC5 cells. Finally, the reduction of these extracellular matrix productions by LRP4-knockdown was rescued by a β-catenin/TCF inhibitor, suggesting that LRP4 is an important regulator for extracellular matrix productions and chondrocyte differentiation by suppressing Wnt/β-catenin signaling.
Volume 451(2)
Pages 302-7
Published 2014-8-22
DOI 10.1016/j.bbrc.2014.07.125
PII S0006-291X(14)01375-8
PMID 25091481
MeSH Adaptor Proteins, Signal Transducing Animals Cell Differentiation / drug effects Cell Differentiation / genetics Cell Differentiation / physiology Cell Line Cells, Cultured Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism* Chondrogenesis / drug effects Chondrogenesis / genetics Chondrogenesis / physiology Extracellular Matrix Proteins / biosynthesis Gene Expression Regulation, Developmental Gene Knockdown Techniques Glycoproteins / genetics Glycosaminoglycans / biosynthesis Growth Plate / growth & development Growth Plate / metabolism Humans Intercellular Signaling Peptides and Proteins / genetics LDL-Receptor Related Proteins / genetics LDL-Receptor Related Proteins / metabolism Mice Mice, Inbred ICR Quercetin / pharmacology RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, LDL / antagonists & inhibitors Receptors, LDL / genetics Receptors, LDL / metabolism* Recombinant Proteins / genetics Recombinant Proteins / metabolism SOX9 Transcription Factor / genetics Wnt Signaling Pathway / drug effects beta Catenin / metabolism
IF 2.985
Times Cited 14
Human and Animal Cells ATDC5(RCB0565)