Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3.

Runx2 and Sp7 are essential transcription factors for osteoblast differentiation. However, the molecular mechanisms responsible for the proliferation of osteoblast progenitors remain unclear. The early onset of Runx2 expression caused limb defects through the Fgfr1-3 regulation by Runx2.

Cbfb2 Isoform Dominates More Potent Cbfb1 and Is Required for Skeletal Development.

Cbfb is a cotranscription factor that forms a heterodimer with Runx proteins Runx1, Runx2, and Runx3. It is required for fetal liver hematopoiesis and skeletal development. Cbfb has two functional isoforms, Cbfb1 and Cbfb2, which are formed by alternative splicing.

Cbfb regulates bone development by stabilizing Runx family proteins.

Runx family proteins, Runx1, Runx2, and Runx3, play important roles in skeletal development. Runx2 is required for osteoblast differentiation and chondrocyte maturation, and haplodeficiency of RUNX2 causes cleidocranial dysplasia, which is characterized by open fontanelles and sutures and hypoplastic clavicles. Cbfb forms a heterodimer with Runx family proteins and enhances their DNA-binding capacity.

Dlx5 and mef2 regulate a novel runx2 enhancer for osteoblast-specific expression.

Runx2 is essential for osteoblast differentiation and chondrocyte maturation. The expression of Runx2 is the first requisite step for the lineage determination from mesenchymal stem cells to osteoblasts. Although the transcript from Runx2 distal promoter is majorly expressed in osteoblasts, the promoter failed to direct green fluorescent protein (GFP) expression to osteoblasts.

Galnt3 deficiency disrupts acrosome formation and leads to oligoasthenoteratozoospermia.

Galnt3 belongs to the GalNAc transferase gene family involved in the initiation of mucin-type O-glycosylation. Male Galnt3-deficient (Galnt3(-/-)) mice were infertile, as previously reported by Ichikawa et al. (2009).

Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1alpha,25-dihydroxyvitamin D3 synthesis in leptin-deficient mice.

Leptin is the LEP (ob) gene product secreted by adipocytes. We previously reported that leptin decreases renal expression of the 25-hydroxyvitamin D(3) 1alpha-hydroxylase (CYP27B1) gene through the leptin receptor (ObRb) by indirectly acting on the proximal tubules. This study focused on bone-derived fibroblast growth factor 23 (FGF-23) as a mediator of the influence of leptin on renal 1alpha-hydroxylase mRNA expression in leptin-deficient ob/ob mice.

Identification of the promoter region of the parathyroid hormone receptor gene responsible for transcriptional suppression by insulin-like growth factor-I.

We investigated parathyroid hormone (PTH)/PTH-related protein receptor (PTH1R) gene suppression induced by insulin-like growth factor (IGF)-I using a rat osteoblast-like cell line (UMR-106). Observations were made with PD98059, a specific ERK signaling pathway inhibitor, and UMR-106 cells transfected with dominant negative or constitutively active forms of MAP kinase kinase. IGF-I inhibited PTH1R gene expression via an ERK1/2 MAP kinase pathway.

Atorvastatin enhances bone density in ovariectomized rats given 17beta-estradiol or human parathyroid hormone(1-34).

We investigated the in vivo effect of atorvastatin on bone mineral density (BMD) in ovariectomized (OVX) rats. Eight-week-old female rats underwent either a sham operation or ovariectomy, and treatments with vehicle, atorvastatin, 17beta-estradiol (E2) and human parathyroid hormone(1-34) [hPTH(1-34)] were initiated 6 wk after the surgery. E2 (10 microg/kg) treatment for 12 wk significantly increased lumbar BMD (L2-L4), whereas atorvastatin did not affect lumbar BMD.

Leptin corrects increased gene expression of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase and -24-hydroxylase in leptin-deficient, ob/ob mice.

Leptin, the ob gene product secreted by adipocytes, controls overall energy balance. We investigated leptin effects on bone metabolism using male leptin-deficient obese (ob/ob) mice, which had lower bone mineral density (BMD) and shorter femurs than lean (?/+) controls. Serum concentrations of calcium, phosphate, tartrate-resistant acid phosphatase (a bone resorption marker) and alkaline phosphatase, and urinary calcium and phosphate excretion were significantly elevated in ob/ob mice, whereas urinary concentrations of deoxypyridinoline did not differed between ob/ob and control mice.

Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation.

Statins such as simvastatin are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that inhibit cholesterol synthesis. We presently investigated statin effects on vascular endothelial growth factor (VEGF) expression in osteoblastic cells. Hydrophobic statins including simvastatin, atorvastatin, and cerivastatin-but not a hydrophilic statin, pravastatin-markedly increased VEGF mRNA abundance in nontransformed osteoblastic cells (MC3T3-E1).

Dexamethasone enhances vitamin D-24-hydroxylase expression in osteoblastic (UMR-106) and renal (LLC-PK1) cells treated with 1alpha,25-dihydroxyvitamin D3.

Chronic glucocorticoid therapy causes rapid bone loss and clinical osteoporosis. We previously found that dexamethasone, a potent glucocorticoid, increased renal expression of vitamin D-24-hydroxylase, which degrades such vitamin D metabolites as 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3). We therefore investigated the mechanisms of this increase in UMR-106 osteoblast-like cells and LLC-PK1 kidney cells.