Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2013) 1 PP167 | DOI: 10.1530/boneabs.1.PP167

ECTS2013 Poster Presentations Cell biology: osteoblasts and bone formation (50 abstracts)

Adipogenesis occurs at the expense of osteoblast differentiation in primary osteoblasts deficient in protease-activated receptor 2

Pamuditha Kularathna 1 , Charles N Pagel 1 , John D Hooper 2 & Eleanor J Mackie 1

1Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia; 2Mater Medical Research Institute, South Brisbane, Queensland, Australia.

The G protein-coupled receptor, protease-activated receptor 2 (PAR2), is expressed by osteoblasts and required for normal skeletal growth and repair. Prostate cancer (PCa) cells commonly secrete proteolytic activators of PAR2 (including matriptase and kallikrein-related peptidase 4) and frequently form osteogenic metastases in bone. This study was undertaken to investigate the hypothesis that PAR2 activators released by PCa cells modulate osteoblast behaviour in such a way as to support the formation of osteogenic metastases. Primary calvarial osteoblasts derived from wild-type (WT) and PAR2-null mice were cultured in medium conditioned by the MDA-PCa-2b cell line (MDA-CM); proliferation was assessed by BrdU incorporation, and differentiation was assessed using assays for alkaline phosphatase activity and mineralization, and quantitative PCR analysis of osteoblast-associated genes. MDA-CM stimulated proliferation of osteoblasts independently of PAR2, but promoted osteoblast differentiation in a PAR2-dependent manner. Alkaline phosphatase activity and expression of Runx2 and Col1 mRNA in 1-day cultures, and mineralization in long-term cultures were all stimulated by MDA-CM in WT but not in PAR2-null osteoblast cultures. A surprising observation was that long-term cultures of MDA-CM-treated PAR2-null osteoblasts contained significantly more adipocytes than did matching WT cultures. In agreement with this observation, MDA-CM stimulated expression of the adipogenesis-associated genes encoding peroxisome proliferator-activated receptor-γ (Pparγ) and lipoprotein lipase (Lpl) in 4-day cultures of PAR2-null but not WT osteoblasts. Moreover, expression of Pparγ mRNA was significantly greater in untreated PAR2-null cultures than in WT cultures. These results indicate that expression of PAR2 favours osteoblast differentiation over adipogenesis in mesenchymal cells capable of both osteoblast and adipocyte differentiation.

Volume 1

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

European Calcified Tissue Society 

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