Regulation of human osteoclast differentiation by thioredoxin binding protein-2 and redox-sensitive signaling.

Unlabelled: Differential expression of TBP-2 and Trx-1 occurs during osteoclastogenesis. Adenoviral overexpression of TBP-2 in osteoclast precursors inhibits Trx-1 expression, osteoclast formation, and AP-1 binding activity. TBP-2 and Trx-1 are key regulators of osteoclastogenesis.

Adenoviral down-regulation of osteopontin inhibits human osteoclast differentiation in vitro.

Although osteopontin (OPN) is highly expressed in osteoclasts, OPN-deficient mice have a near-normal bone phenotype and its role in osteoclast differentiation and function remains uncertain. We used an adenoviral OPN-antisense vector (AdOPN-AS) to down-regulate OPN expression in a human in vitro osteoclastogenesis model employing CFU-GM precursors treated with RANKL and M-CSF. Cultures infected with AdOPN-AS showed reduced secretion of OPN compared to cultures infected with a control adenoviral vector expressing beta-galactosidase.

Osteoclastic potential of human CFU-GM: biphasic effect of GM-CSF.

Unlabelled: Human osteoclasts can be efficiently generated in vitro from cord blood mononuclear cells and derived CFU-GM colonies. However, CFU-M colonies are poorly osteoclastogenic. Short-term (2-48 h) treatment with GM-CSF stimulates osteoclast formation by proliferating precursors, whereas longer exposure favors dendritic cell formation.

Gene array identification of osteoclast genes: differential inhibition of osteoclastogenesis by cyclosporin A and granulocyte macrophage colony stimulating factor.

Treatment of adherent peripheral blood mononuclear cells (PBMCs) with macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL) stimulates the formation of multinucleate osteoclast-like cells. Treatment with M-CSF alone results in the formation of macrophage-like cells. Through the use of Atlas human cDNA expression arrays, genes regulated by RANKL were identified.

Leptin inhibits osteoclast generation.

Originally, leptin was described as a product of adipocytes that acts on the hypothalamus to regulate appetite. However, subsequently, it has been shown that leptin receptors are distributed widely and that leptin has diverse functions, including promotion of hemopoietic and osteoblastic differentiation. It has been recognized for some time that both serum leptin and bone mass are correlated positively to body fat mass and, recently, we have shown a direct positive relationship between serum leptin and bone mass in nonobese women.