Characterization of Osteocrin Expression in Human Bone

Sharyn Bord ¹, Deborah C. Ireland ¹, Pierre Moffatt ¹, Gethin P. Thomas ¹ and Juliet E. Compston ^1*

¹ Cambridge University School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom (SB,DCI,JEC), and Phenogene Therapeutics Inc., Montreal, Quebec, Canada (PM,GPT)

^* To whom correspondence should be addressed. E-mail: jec1001{at}cam.ac.uk.

Submitted on October 26, 2004
Accepted on 4 May 2005

	Abstract

Osteocrin, a bone-active molecule, has been shown in animals to be highly expressed in cells of the osteoblast lineage. We have characterised this protein in human cultured primary human osteoblasts, in developing human neonatal bone and in iliac crest bone biopsies from adult women. In vivo, osteocrin expression was localized in developing human neonatal rib bone, with intense immunoreactivity in osteoblasts on bone forming surfaces, in newly incorporated osteocytes and in some late hypertrophic chondrocytes. In adult bone, osteocrin expression was specifically localized to osteoblasts and young osteocytes at bone forming sites. In vitro, osteocrin expression decreased time-dependently (p<0.02) in osteoblasts cultured for 2, 3 and 6 days. Expression was further decreased in cultures containing 200 nM hydrocortisone by 1.5-, 2.3- and 3.1-fold (p<0.05) at the same time points. In contrast, alkaline phosphatase expression increased with osteoblast differentiation (p<0.05). Low-dose oestradiol decreased osteocrin expression time-dependently (p<0.05), while osteocrin expression in cultures treated with high-dose oestradiol was not significantly changed. These results demonstrate that osteocrin is expressed in human skeletal tissue, particularly in osteoblasts in developing bone and at sites of bone remodelling, suggesting a role in bone formation. Thus osteocrin provides a marker of osteoblast lineage cells and appears to correlate with osteoblast activity.

Key Words: osteocrin, ostn, osteoblasts, osteocytes, human bone formation

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