title: Presence of messenger ribonucleic acid encoding osteocalcin, a marker of bone turnover, in bone marrow megakaryocytes and peripheral blood platelets.
abstract: Osteocalcin (Oc), an abundant gamma-carboxylated protein (mol wt, 5800) of bone matrix, is used as a serum marker of bone turnover because it is considered to be uniquely synthesized by the osteoblast. Our finding of Oc messenger RNA (mRNA) in rat tibial diaphyseal marrow led us to investigate the cellular origins of Oc mRNA in peripheral blood and bone marrow. In anticoagulated blood, Oc mRNA was detected in total RNA prepared from buffy coat cells (BCC). Fractionation of rat and human blood showed that platelets contain Oc mRNA identical to that found in bone cells. In rat bone marrow, Oc mRNA is highly enriched in the platelet-producing megakaryocyte population. Depending upon the RIA used, immunoreactive Oc was either undetectable or present at very low levels in platelets and megakaryocytes, suggesting that synthesis of Oc by these cells may be under strong translational regulation. In addition, Oc levels were higher in serum vs. plasma obtained from the same blood, suggesting that Oc may be released by platelets during blood clotting. Interestingly, the magnitude of this difference was greater in female rats. Injection of 1,25-dihydroxyvitamin D3 dose-dependently increased plasma Oc, but did not cause correlative changes in steady state levels of Oc mRNA in BCC. During rat growth, plasma Oc was maximal, whereas Oc mRNA levels in BBC were low. This relationship was reversed during aging. A correlation between Oc mRNA levels in BCC and rat age suggests a developmental regulation of Oc mRNA levels in platelets. These data indicate that Oc mRNA is not restricted to cells on mineralizing surfaces, but is also found in megakaryocytes and peripheral blood platelets, which possibly contribute to the Oc levels in blood and the regulation of bone turnover.
authors.affiliation: Department of Cardiovascular and Metabolic Diseases, Pfizer, Inc., Groton, Connecticut 06340.
authors.forename: M A
authors.initials: MA
authors.lastname: Thiede
authors.forename: S L
authors.initials: SL
authors.lastname: Smock
authors.forename: D N
authors.initials: DN
authors.lastname: Petersen
authors.forename: W A
authors.initials: WA
authors.lastname: Grasser
authors.forename: D D
authors.initials: DD
authors.lastname: Thompson
authors.forename: S K
authors.initials: SK
authors.lastname: Nishimoto
mesh_terms: D000328:Adult; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D001842:Bone and Bones / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism*; D013010:Sonication
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D015675:Osteocalcin; D002117:Calcitriol