Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Inhibition of osteoclastogenesis by the fatty acid analogue triazolyl-PA (#322)

Jian-ming Lin 1 , Dorit Naot 1 , David Musson 1 , William A Denny 2 , Jillian Cornish 1
  1. Department of Medicine, University of Auckland, Auckland, N/A, New Zealand
  2. Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Auckland, N/A, New Zealand

Palmitic acid was shown to inhibit osteoclastogenesis in vitro, but its potential therapeutic use as an inhibitor of bone resorption is limited by its modest potency, poor aqueous solubility and rapid metabolism. We have developed a number of fatty acid analogues and determined their effects on the formation of tartrate resistant acid phosphatase-positive multinucleated cells (TRAP+ve MNC) in mouse bone marrow cultures and in RAW264.7 cells. One of the analogues, produced by the insertion of a triazole unit into palmitic acid (triazolyl-PA), had much greater potency than palmitic acid in inhibiting the formation of TRAP+ve MNC in mouse bone marrow cultures and in RAW264.7 cells. In the current study, the effect of triazolyl-PA was further characterised by analysis of the expression of key osteoclast genes in mouse bone marrow cultures. Bone marrow cells were cultured in the presence of 1,25-dihydroxyvitamin D3, and treated with 10 µg/mL triazolyl-PA or vehicle control. Gene expression analysis has shown that the osteoclast marker/regulator genes TRAP, DC-STAMP and NFATc1 were up-regulated in the control cultures, but triazolyl-PA treatment attenuated the induction of their expression. The expression of the known stimulators of osteoclastogenesis, TNF and CTGF was reduced in the treated cells and the expression of both RANKL and OPG were mildly inhibited by triazolyl-PA. Our study found that triazolyl-PA inhibits the expression of key osteoclast markers and osteoclastogenesis modulators. Further investigations of this analogue will determine the potential of its development as a therapeutic agent for inhibition of bone resorption.