DEMONSTRATION OF VITAMIN-D-RECEPTOR TRANSCRIPTS IN ACTIVELY RESORBINGOSTEOCLASTS IN BONE SECTIONS

The effects of the active metabolite of vitamin D, 1,25 dihydroxyvitam in D-3 (1,25D), are mediated via the vitamin D receptor (VDR), 1,25D i s known to have profound effects on bone resorption, but proof that th e human osteoclast expresses VDR in vivo is absent, Receptors have bee n demonstrated in osteoblasts, and it has been generally accepted that the effects of 1,25D on formed osteoclasts are mediated via osteoblas ts. Using conventional riboprobe in situ hybridization, VDR transcript s were readily detectable in osteoblasts within sections taken from no rmal bone and several actively remodelling bone tissues, namely, Paget 's disease, renal hyperparathyroidism, and healing fracture callus, Ho wever, VDR transcripts also appeared to be present at low levels withi n osteoclasts from two pagetic samples and two hyperparathyroid sample s, To examine this latter finding further, we have used the novel tech nique of in situ-reverse transcriptase-polymerase chain reaction (IS-R T-PCR) for specific amplification and detection of VDR mRNA within sec tions taken from the same conditions described above, and also from os teoclastoma samples, As expected, VDR transcripts were amplified and d etected in osteoblasts and marrow cells, but were also prominently fou nd in osteoclasts at approximately 50% of the level detected in osteob lasts in normal bone and at 60% in the active bone tissues, This sugge sts that in addition to effects on osteoclast precursors and those med iated via osteoblasts, 1,25D could exert direct effects on the active bone resorbing cells in vivo.