RRC ID 61972
Author Takegami Y, Ohkawara B, Ito M, Masuda A, Nakashima H, Ishiguro N, Ohno K.
Title R-spondin 2 facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification.
Journal Biochem Biophys Res Commun
Abstract Endochondral ossification is a crucial process for longitudinal growth of bones. Differentiating chondrocytes in growth cartilage form four sequential zones of proliferation, alignment into column, hypertrophy, and substitution of chondrocytes with osteoblasts. Wnt/β-catenin signaling is essential for differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. R-spondin 2 (Rspo2), a member of R-spondin family, is an agonist for Wnt signaling, but its role in chondrocyte differentiation remains unknown. Here we report that growth cartilage of Rspo2-knockout mice shows a decreased amount of β-catenin and increased amounts collagen type II (CII) and Sox9 in the abnormally extended proliferating zone. In contrast, expression of collagen type X (CX) in the hypertrophic zone remains unchanged. Differentiating chondrogenic ATDC5 cells, mimicking proliferating chondrocytes, upregulate Rspo2 and its putative receptor, Lgr5, in parallel. Addition of recombinant human Rspo2 to differentiating ATDC5 cells decreases expressions of Col2a1, Sox9, and Acan, as well as production of proteoglycans. In contrast, lentivirus-mediated knockdown of Rspo2 has the opposite effect. The effect of Rspo2 on chondrogenic differentiation is mediated by Wnt/β-catenin signaling, and not by Wnt/PCP or Wnt/Ca(2+) signaling. We propose that Rspo2 activates Wnt/β-catenin signaling to reduce Col2a1 and Sox9 and to facilitate differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage.
Volume 473(1)
Pages 255-264
Published 2016-4-22
DOI 10.1016/j.bbrc.2016.03.089
PII S0006-291X(16)30400-4
PMID 27012200
MeSH Animals Cartilage / metabolism Cell Differentiation Cell Proliferation Chondrocytes / cytology* Collagen Type II / metabolism* Female Gene Expression Regulation Humans Immunohistochemistry Intercellular Signaling Peptides and Proteins / metabolism Mice Mice, Knockout Receptors, G-Protein-Coupled / metabolism SOX9 Transcription Factor / metabolism* Thrombospondins / metabolism* Transcription Factors / metabolism Wnt Proteins / metabolism Wnt Signaling Pathway* beta Catenin / metabolism
IF 2.985
Human and Animal Cells ATDC5(RCB0565)