Int J Oral Biol.  2011 Dec;36(4):173-178.

TNFalpha Increases the Expression of beta2 Adrenergic Receptors in Osteoblasts

• Baek K
• Lee HL
• Hwang HR
• Park HJ
• Kwon A
• Qadir AS
• Baek JH

Abstract

Tumor necrosis factor alpha (TNFalpha) is a multifunctional cytokine that is elevated in inflammatory diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Recent evidence has suggested that beta2 adrenergic receptor (beta2AR) activation in osteoblasts suppresses osteogenic activity. In the present study, we explored whether TNFalpha modulates betaAR expression in osteoblastic cells and whether this regulation is associated with the inhibition of osteoblast differentiation by TNFalpha. In the experiments, we used C2C12 cells, MC3T3-E1 cells and primary cultured mouse bone marrow stromal cells. Among the three subtypes of betaAR, beta2 and beta3AR were found in our analysis to be upregulated by TNFalpha. Moreover, isoproterenol-induced cAMP production was observed to be significantly enhanced in TNFalpha-primed C2C12 cells, indicating that TNFalpha enhances beta2AR signaling in osteoblasts. TNFalpha was further found in C2C12 cells to suppress bone morphogenetic protein 2-induced alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes including Runx2, ALP and osteocalcin. Propranolol, a beta2AR antagonist, attenuated this TNFalpha suppression of osteogenic differentiation. TNFalpha increased the expression of receptor activator of NF-kappaB ligand (RANKL), an essential osteoclastogenic factor, in C2C12 cells which was again blocked by propranolol. In summary, our data show that TNFalpha increases beta2AR expression in osteoblasts and that a blockade of beta2AR attenuates the suppression of osteogenic differentiation and stimulation of RANKL expression by TNFalpha. These findings imply that a crosstalk between TNFalpha and beta2AR signaling pathways might occur in osteoblasts to modulate their function.

Keyword

TNFalpha; beta2 adrenergic receptor; osteoblasts

MeSH Terms

Alkaline Phosphatase
Animals
Arthritis, Rheumatoid
Atherosclerosis
Bone Morphogenetic Proteins
Durapatite
Mesenchymal Stromal Cells
Mice
Osteoblasts
Osteocalcin
Propranolol
Receptor Activator of Nuclear Factor-kappa B
Receptors, Adrenergic
Tumor Necrosis Factor-alpha
Alkaline Phosphatase
Bone Morphogenetic Proteins
Durapatite
Osteocalcin
Propranolol
Receptor Activator of Nuclear Factor-kappa B
Receptors, Adrenergic
Tumor Necrosis Factor-alpha