Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation (J Clin Invest, 2012, doi:10.1172/JCI61209)

報告日期: 2012/11/27
報告時間: 15:10~16:00
報告學生: 蔡耀宗
講評老師: 蔡曜聲
附件下載: 下載[1258-1350711944-1.pdf] 

Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation

The Journal of Clinical Investigation Volume 122 Number 9 September 2012

Speaker: Yao-Tsung Tsai                                    Date: 2012.11.27

                           Commentator: Yau-Sheng Tsai, Ph.D.               Room: 602

Abstract:

Osteoporosis is one of the common problems in the aging population. The major symptoms of osteoporosis are reduction of spongy bone mass and bone mineral density(1). Osteoporosis also accompanies replacement of bone marrow fat. Previous studies shown that bone marrow cells from osteoporotic patients tended to differentiate into adipocytes(2). However, the definite mechanisms of the fates of bone marrow cells are unclear. In previous reports, VEGF has been found that highly expressed in osteoblastic precursor cells and stimulated bone formation(3). The authors hypothesized that VEGF may play an important regulator between osteoblast and adipocyte differentiaton. In this study, the authors shown that mice with conditional VEGF deficiency in osteoblast lineage exhibited an osteoporosis-like phenotype including reduction of bone mass and increased bone marrow fat. Furthermore, knockdown of Vegf decreased osteoblast and increased adipocyte differentiation. Osteoblast differentiation was reduced when VEGF receptor 1 or 2 was knocked down. However, treatment with recombinant VEGF or VEGF neutralizing antibodies didn't affect osteoblast or adipocyte differentiation. These results suggested that VEGF may regulate differentiation in mesenchymal stem cells through intracrine mechanism. In addition, the authors also found that VEGF affected the fates of mesenchymal stem cells by regulating RUNX2 and PPARγ2 as well as through an interaction with lamin A/C. The mechanism of intracrine VEGF which regulated adipocyte and osteoblast differentiation may be a potential therapeutic target for bone loss in osteoporosis.

References:

1.Rodríguez JP, Montecinos L. Mesenchymal stem cells from osteoporotic patients produce a type I collagen-deficient extracellular matrix favoring adipogenic differentiation. J Cell Biochem. 2000;79(4):557–565.

2.Justesen J, Stenderup K. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2001; 2(3):165–171.

3. Mayr-Wohlfart U, et al. Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone. 2002;30(3):472–477.