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Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype.
J Biol Chem. 2003 Dec 12; 278(50):50563-71.JB

Abstract

Although a number of secreted factors have been demonstrated to be bone regulators, none of these are unique to bone. Using a viral-based signal-trap strategy we have identified a novel gene we have termed "osteocrin." A 1280-bp mRNA encodes osteocrin producing a mature protein of 103 amino acids with a molecular mass of 11.4 kDa. Osteocrin shows no homology with any known gene except for two conserved sequence motifs reminiscent of dibasic cleavage sites found in peptide hormone precursors. Immunofluorescence and Western blot analysis confirmed the secretory nature of osteocrin. Two protein species were identified in the medium of cells overexpressing osteocrin, a full-length 11.4 kDa species and a processed approximately 5 kDa species. Mutation of the 76KKKR79 dibasic cleavage site abolished the appearance of this smaller osteocrin fragment. By in situ hybridization in mouse embryos, osteocrin was expressed specifically in Cbfa-1-positive, osteocalcin-negative osteoblasts. Immunohistochemistry on adult mouse bone showed osteocrin localization in osteoblasts and young osteocytes. By Northern blot analysis, osteocrin expression was only detected in bone, expression peaking just after birth and decreasing markedly with age. In primary osteoblastic cell cultures osteocrin expression coincided with matrix formation then decreased in very mature cultures. Treatment of cultures with 1,25-dihydroxyvitamin D3 resulted in a rapid dose-dependent down-regulation of osteocrin expression, suggesting direct regulation. Chronic treatment of primary cultures with osteocrin-conditioned media inhibited mineralization and reduced osteocalcin and alkaline phosphatase expression. These results suggest that osteocrin represents a novel, unique vitamin D-regulated bone-specific protein that appears to act as a soluble osteoblast regulator.

Authors+Show Affiliations

Phenogene Therapeutics Inc., 416 de Maisonneuve West, Suite 1020, Montreal, Quebec H3A 1L2, Canada. gthomas@phenogene.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14523025

Citation

Thomas, Gethin, et al. "Osteocrin, a Novel Bone-specific Secreted Protein That Modulates the Osteoblast Phenotype." The Journal of Biological Chemistry, vol. 278, no. 50, 2003, pp. 50563-71.
Thomas G, Moffatt P, Salois P, et al. Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. J Biol Chem. 2003;278(50):50563-71.
Thomas, G., Moffatt, P., Salois, P., Gaumond, M. H., Gingras, R., Godin, E., Miao, D., Goltzman, D., & Lanctôt, C. (2003). Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. The Journal of Biological Chemistry, 278(50), 50563-71.
Thomas G, et al. Osteocrin, a Novel Bone-specific Secreted Protein That Modulates the Osteoblast Phenotype. J Biol Chem. 2003 Dec 12;278(50):50563-71. PubMed PMID: 14523025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. AU - Thomas,Gethin, AU - Moffatt,Pierre, AU - Salois,Patrick, AU - Gaumond,Marie-Hélène, AU - Gingras,Rock, AU - Godin,Eric, AU - Miao,Dengshun, AU - Goltzman,David, AU - Lanctôt,Christian, Y1 - 2003/10/01/ PY - 2003/10/3/pubmed PY - 2004/1/16/medline PY - 2003/10/3/entrez SP - 50563 EP - 71 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 278 IS - 50 N2 - Although a number of secreted factors have been demonstrated to be bone regulators, none of these are unique to bone. Using a viral-based signal-trap strategy we have identified a novel gene we have termed "osteocrin." A 1280-bp mRNA encodes osteocrin producing a mature protein of 103 amino acids with a molecular mass of 11.4 kDa. Osteocrin shows no homology with any known gene except for two conserved sequence motifs reminiscent of dibasic cleavage sites found in peptide hormone precursors. Immunofluorescence and Western blot analysis confirmed the secretory nature of osteocrin. Two protein species were identified in the medium of cells overexpressing osteocrin, a full-length 11.4 kDa species and a processed approximately 5 kDa species. Mutation of the 76KKKR79 dibasic cleavage site abolished the appearance of this smaller osteocrin fragment. By in situ hybridization in mouse embryos, osteocrin was expressed specifically in Cbfa-1-positive, osteocalcin-negative osteoblasts. Immunohistochemistry on adult mouse bone showed osteocrin localization in osteoblasts and young osteocytes. By Northern blot analysis, osteocrin expression was only detected in bone, expression peaking just after birth and decreasing markedly with age. In primary osteoblastic cell cultures osteocrin expression coincided with matrix formation then decreased in very mature cultures. Treatment of cultures with 1,25-dihydroxyvitamin D3 resulted in a rapid dose-dependent down-regulation of osteocrin expression, suggesting direct regulation. Chronic treatment of primary cultures with osteocrin-conditioned media inhibited mineralization and reduced osteocalcin and alkaline phosphatase expression. These results suggest that osteocrin represents a novel, unique vitamin D-regulated bone-specific protein that appears to act as a soluble osteoblast regulator. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/14523025/Osteocrin_a_novel_bone_specific_secreted_protein_that_modulates_the_osteoblast_phenotype_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=14523025 DB - PRIME DP - Unbound Medicine ER -