ECTS Abstracts (2015) 1 P169

Tumour Necrosis Factor-Alpha Downregulates Uncarboxylated Osteocalcin Secretion via Beta Adrenergic Signalling Pathway in Osteoblasts

Kyunghwa Baek1,2, Dan Bi Park1,2, Jeong-Hwa Baek3,4 & Seong-Hee Ko1,2

1Department of Pharmacology,College of Dentistry, Gangneung-Wonju National University, Gangneung, Republic of Korea; 2Research Institute of Oral Science, Gangneung-Wonju National University, Gangneung, Republic of Korea; 3Department of Molecular Genetics, School of Dentistry, Seoul National University, Seoul, Republic of Korea; 4Dental Research Institute, Seoul National University, Seoul, Republic of Korea.

Emerging evidence has suggested important endocrine roles of bone, communicating with other tissues for regulating body energy metabolism. It’s been reported that sympathetic nervous system (SNS) activation induces expression of the Esp gene, exclusive to osteoblasts, where Esp gene regulates osteoblastic secretion of the hormone-like substance osteocalcin. An undercarboxylated form of osteocalcin acts as a regulator of insulin in the pancreas. TNF-α is a multifunctional proinflammatory cytokine. Obesity, diabetes and related bone loss is associated with chronic ‘inflammation’ characterised by abnormal cytokine production such as TNF-α from T cell. We previously reported that TNFα upregulates beta2-adrenergic receptor (β2AR) expression in murine osteoblastic cells and that this modulation is associated with TNFα inhibition of osteoblast differentiation. However the regulatory role of TNF-α in bioactive osteocalcin secretion in osteoblasts has not been investigated. In the present study, we investigated 1) whether TNF-α induces Esp, gene expressions in osteoblast and/or thereby decrease in bioactive osteocalcin and 2) whether down-regulation of TNF-α mediated sympathetic tone with βAR antagonist, propranolol could regulate Esp expression and/or bioactive osteocalcin secretion. C2C12, a murine mesenchymal precursor cell line was used in this study. Real time PCR and western blot analysis was performed to assess β2AR and Esp gene expressions. For bioactive osteocalcin level measurement, undercarboxylated osteocalcin ELISA assay was conducted. TNFα upregulates β2AR expression in C2C12 cells. Esp expression in C2C12 cells was also upregulated by TNFα treatment, and this increment was attenuated by propranolol. Bioactive osteocalcin level decreased with TNFα treatment and this decrease was mitigated with propranolol treatment. In summary, activation of TNFα signalling in osteoblastic cells downregulates bioactive osteocalcin secretion, partially via βAR signalling pathway. These findings imply that a crosstalk between TNFα and βAR signalling pathways might occur in osteoblasts to modulate body energy metabolism.

Disclosure: The authors declared no competing interests. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) 2014010086.

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