GSBS Student Publications

Title

Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced chondrocyte differentiation

GSBS Program

Cell Biology

UMMS Affiliation

Department of Cell Biology; Department of Orthopedics and Physical Rehabilitation

Date

4-1-2006

Document Type

Article

Medical Subject Headings

Animals; Blotting, Western; Bone Morphogenetic Proteins; Cell Differentiation; Cells, Cultured; Chondrocytes; Collagen Type II; Collagen Type X; Core Binding Factor Alpha 1 Subunit; Fibroblasts; Gene Expression Profiling; Gene Expression Regulation, Developmental; Growth Plate; Hedgehog Proteins; High Mobility Group Proteins; Hypertrophy; Immunohistochemistry; Intercellular Signaling Peptides and; Proteins; Membrane Proteins; Mice; Mice, Knockout; Osteogenesis; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Trans-Activators; Transcription Factors; Transforming Growth Factor beta; Wnt Proteins; beta Catenin

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

Canonical Wnt signaling (beta-catenin/TCF) has emerged as a key regulator of skeletogenesis. In this study, chondrogenesis is examined in a mouse model in which the Wnt antagonist secreted frizzled related protein 1 (sFRP1) is non-functional and results in a high bone mass phenotype and activation through the canonical pathway of the Runx2 transcription factor that is essential for bone formation. We find during the period of rapid post-natal growth, shortened height of the growth plate and increased calcification of the hypertrophic zone (HZ) in the sFRP1-/- mouse, indicating accelerated endochondral ossification. Using mouse embryo fibroblasts (MEFs) induced into the chondrogenic lineage, increased chondrogenesis and accelerating differentiation of hypertrophic chondrocytes in the sFRP1-/- MEFs was observed compared to WT cells. The induced maturation of hypertrophic chondrocytes in sFRP1(-/-) MEFs was inversely correlated to phospho-beta-catenin levels, indicating involvement of activated canonical Wnt signaling characterized by an increased expression of collagen type 2a1 and Sox 9. However, an absence of Indian hedgehog expression which occurs in WT cells was found. SFRP1-/- cells also exhibited an early induction of collagen type 10a1. Thus, these modifications in gene expression are contributing mechanism(s) for increased chondrocyte differentiation in SFRP1-/- cells. These studies have identified sFRP1 as a critical negative regulator of Wnt signaling for the normal progression of chondrocyte differentiation. Microarray gene profiling provided additional novel insights into the regulatory factors for appropriate Wnt signaling necessary for the control of chondrocyte maturation.

Rights and Permissions

Citation: J Cell Physiol. 2006 Jul;208(1):87-96. Link to article on publisher's site

DOI of Published Version

10.1002/jcp.20637

Related Resources

Link to article in PubMed

Journal Title

Journal of cellular physiology

PubMed ID

16575902