Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice.

PPARγ has critical role in the differentiation of mesenchymal stem cells into adipocytes while suppressing osteoblastic differentiation. We generated transgenic mice that overexpress PPARγ specifically in osteoblasts under the control of a 2.3-kb procollagen type 1 promoter (Col.

Wnt inhibitory factor (WIF)-1 inhibits osteoblastic differentiation in mouse embryonic mesenchymal cells.

Wnt inhibitory factor (WIF)-1 belongs to the members of secreted modulators of Wnt proteins. Secreted frizzled-related proteins (sFRPs), another member of Wnt modulators, have been shown to play differential roles in Wnt signaling depending on the subtypes and cell models. This study was undertaken to investigate the functional role of WIF-1 in osteoblastic differentiation of mouse mesenchymal C3H10T1/2 cells.

Differential effects of secreted frizzled-related proteins (sFRPs) on osteoblastic differentiation of mouse mesenchymal cells and apoptosis of osteoblasts.

Secreted frizzled-related proteins (sFRPs) are modulators of Wnt signaling. This study was undertaken for definitive assessment of contribution of different sFRPs in osteoblastic differentiation of mesenchymal progenitor cells and apoptosis of osteoblasts. Treatment of C3H10T1/2 cells with sFRP-2 at concentrations of 10, 50, and 100nM and sFRP-4 at low concentrations (5nM) significantly increased Wnt-3A-induced alkaline phosphatase (ALP) activities, whereas sFRP-1 or 3 did not.

CCAAT/enhancer-binding protein delta activates the Runx2-mediated transcription of mouse osteocalcin II promoter.

CCAAT/enhancer-binding proteins (C/EBPs) are involved in the regulation of cell proliferation, differentiation, and control of metabolic function. Although the roles of C/EBPs in osteoblasts are largely unknown, both C/EBPbeta and -delta have been shown to enhance rat osteocalcin promoter activity through the synergistic activation of Runx2 at the C/EBP element. Here we show that in the mouse, C/EBPdelta increases the expression of osteocalcin whereas C/EBPbeta does not.

Retrovirus-mediated gene transfer of receptor activator of nuclear factor-kappaB-Fc prevents bone loss in ovariectomized mice.

Postmenopausal osteoporosis is characterized by increased bone resorption due to estrogen deficiency. Receptor activator of nuclear factor-kappaB-Fc (RANK-Fc), a fusion protein that specifically blocks receptor activator of nuclear factor ligand binding to RANK, has been known to be efficient and well tolerated in animal models of osteoporosis. Here we show that cell-based gene therapy with RANK-Fc effectively prevented bone loss in ovariectomized (OVX) mice.

Dominant negative N-cadherin inhibits osteoclast differentiation by interfering with beta-catenin regulation of RANKL, independent of cell-cell adhesion.

Unlabelled: We studied the effects of dominant negative N-cadherin (NCadDeltaC) expression in ST2 cells on their ability to support osteoclastogenesis. Expression of NCadDeltaC in ST2 cells did not decrease cell-to-cell adhesion but significantly reduced osteoclast formation when co-cultured with BMMs. NCadDeltaC inhibited beta-catenin/TCF signaling, resulting in decreased RANKL expression, which could contribute to the reduced osteoclast formation.

Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells.

Ghrelin is a 28-amino-acid peptide identified in the stomach as an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) that strongly stimulates the release of growth hormone at the hypothalamus and pituitary level. Although GHS-Rs are expressed in a variety of peripheral tissues, little is known about its effect on bone independent of GH/IGF-1 axis. This study was undertaken to investigate whether ghrelin exerts a direct effect on osteoblasts.

Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts.

Osteoblasts and adipocytes originate from common mesenchymal progenitor cells. We have investigated whether mouse osteoblastic MC3T3-E1 cells can be induced to transdifferentiate into mature adipocytes by the ectopic expression of adipogenic transcription factors, PPARgamma, C/EBPalpha, or both. Retrovirus-mediated overexpression of PPARgamma alone or both PPARgamma and C/EBPalpha resulted in reduced alkaline phosphatase activity and osteoblast-specific gene expression.

Nordihydroguaiaretic acid, an antioxidant, inhibits transforming growth factor-beta activity through the inhibition of Smad signaling pathway.

Transforming growth factor-beta (TGF-beta) and its family are potent and multi-functional cytokines that affect various fundamental biological events. TGF-beta has a unique signaling pathway that is carried by Smad family, and many recent studies showed the extensive crosstalk between Smad pathway and other signaling pathway. There were also clear evidences for the involvement of oxidative events in TGF-beta signaling pathway.