Literature DB >> 11069730

FrzB-2: a human secreted frizzled-related protein with a potential role in chondrocyte apoptosis.

I E James1, S Kumar, M R Barnes, C J Gress, A T Hand, R A Dodds, J R Connor, B R Bradley, D A Campbell, S E Grabill, K Williams, S M Blake, M Gowen, M W Lark.   

Abstract

OBJECTIVE: To characterize a novel secreted frizzled-related protein (SFRP) and determine its tissue distribution at the mRNA and protein level.
METHODS: The FrzB-2 gene was identified by expressed sequence tag (EST) analysis of human tissue-derived libraries. Tissue distribution of FrzB-2 mRNA was determined by Northern blot analysis and in situ hybridization. FrzB-2 protein reactivity was localized in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody against a peptide sequence unique to FrzB-2. Apoptosis was detected in articular cartilage sections using Tunel staining.
RESULTS: ESTs corresponding to FrzB-2 were found in osteoblast, chondrosarcoma, osteosarcoma, osteoclastoma and synovial fibroblast libraries. FrzB-2 mRNA is expressed in a number of tissues and cell types including bone-related cells and tissues such as primary human osteoblasts and osteoclastoma. In situ hybridization studies showed strong FrzB-2 mRNA expression in human chondrocytes in human osteoarthritic (OA) cartilage but negligible levels in normal cartilage chondrocytes. The FrzB-2 cDNA encodes a secreted 40 kDa protein consisting of 346 amino acids. FrzB-2 is 92. 5% identical to the rat orthologue, DDC-4, which has been shown to be associated with physiological apoptosis. FrzB-2 protein was selectively detected in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody. Consistent with its potential role in apoptosis, positive FrzB-2 staining and Tunel positive nuclei staining were detected in chondrocyte clones in sections of human OA cartilage.
CONCLUSION: These data suggest that FrzB-2 may play a role in apoptosis and that the expression of this protein may be important in the pathogenesis of human OA. Copyright 2000 OsteoArthritis Research Society International.

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Year:  2000        PMID: 11069730     DOI: 10.1053/joca.1999.0321

Source DB:  PubMed          Journal:  Osteoarthritis Cartilage        ISSN: 1063-4584            Impact factor:   6.576


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