Introduction Sheep are being used increasingly for spinal and other skeletal-related research. However, there is still limited information about the molecular pathways of bone remodelling in this species compared to rats or mice. It has been demonstrated in other animal models and in the human that the receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) play major regulatory roles in controlling osteoclast activity and their differentiation. We investigated the expression of RANKL and OPG in trabecular bone of an ovariectomised steroid-treated osteopaenic sheep model.

Methods Trabecular bone from the lumbar spine (LS) and proximal femur (PF) of ten osteopaenic ewes and four normal ewes were collected [1]. Total RNA was isolated and complementary DNA (cDNA) was synthesised. DNA encoding RANKL and OPG were sequenced and ovine specific primers were designed to amplify the cDNA by real time RT-PCR to generate products corresponding to mRNA encoding RANKL and OPG. The results were normalised to 18S RNA.

Results Total OPG expression (in trabecular bone) from the PF region was over two fold higher than the LS (P< 0.0001). The relative expression of OPG in the both LS and PF regions were significantly higher in the treated animals (steroid & oophorectomy) compared to controls (p< 0.05). The relative expression of RANK-L in the PF was significantly higher than in the LS (P< 0.0001). However, the relative RANK-L expression in the treated animals was not significantly different from the control animals in either region. The ratio of RANK-L:OPG in the PF and the LS was not significantly different but it was significantly reduced in the osteopaenic animals.

Discussion Based on this gene expression study and previous histomorphological data, it appears that trabecular bone loss is not due to increased osteoclastic activity but may rather due to lack of osteoblastic activity and function. Higher expression of OPG and RANK-L and greater bone loss compared to LS suggest that the rate of bone turnover is greater in the PF. Further investigation of the molecular pathways of bone loss in this animal model will increase its utility for osteoporosis research.