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Osteocalcin is Necessary for the Alignment of Apatite Crystallites, but Not Glucose Metabolism, Testosterone Synthesis, or Muscle Mass

Overview
Journal PLoS Genet
Specialty Genetics
Date 2020 May 29
PMID 32463816
Citations 83
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Abstract

The strength of bone depends on bone quantity and quality. Osteocalcin (Ocn) is the most abundant noncollagenous protein in bone and is produced by osteoblasts. It has been previously claimed that Ocn inhibits bone formation and also functions as a hormone to regulate insulin secretion in the pancreas, testosterone synthesis in the testes, and muscle mass. We generated Ocn-deficient (Ocn-/-) mice by deleting Bglap and Bglap2. Analysis of Ocn-/-mice revealed that Ocn is not involved in the regulation of bone quantity, glucose metabolism, testosterone synthesis, or muscle mass. The orientation degree of collagen fibrils and size of biological apatite (BAp) crystallites in the c-axis were normal in the Ocn-/-bone. However, the crystallographic orientation of the BAp c-axis, which is normally parallel to collagen fibrils, was severely disrupted, resulting in reduced bone strength. These results demonstrate that Ocn is required for bone quality and strength by adjusting the alignment of BAp crystallites parallel to collagen fibrils; but it does not function as a hormone.

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References
1.
Rueda P, Harley E, Lu Y, Stewart G, Fabb S, Diepenhorst N . Murine GPRC6A Mediates Cellular Responses to L-Amino Acids, but Not Osteocalcin Variants. PLoS One. 2016; 11(1):e0146846. PMC: 4718634. DOI: 10.1371/journal.pone.0146846. View

2.
Pittas A, Harris S, Eliades M, Stark P, Dawson-Hughes B . Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab. 2008; 94(3):827-32. PMC: 2681283. DOI: 10.1210/jc.2008-1422. View

3.
Raghavan M, Sahar N, Wilson R, Mycek M, Pleshko N, Kohn D . Quantitative polarized Raman spectroscopy in highly turbid bone tissue. J Biomed Opt. 2010; 15(3):037001. PMC: 2881928. DOI: 10.1117/1.3426310. View

4.
Diaz-Lopez A, Bullo M, Juanola-Falgarona M, Martinez-Gonzalez M, Estruch R, Covas M . Reduced serum concentrations of carboxylated and undercarboxylated osteocalcin are associated with risk of developing type 2 diabetes mellitus in a high cardiovascular risk population: a nested case-control study. J Clin Endocrinol Metab. 2013; 98(11):4524-31. DOI: 10.1210/jc.2013-2472. View

5.
Lambert L, Challa A, Niu A, Zhou L, Tucholski J, Johnson M . Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology. Dis Model Mech. 2016; 9(10):1169-1179. PMC: 5087831. DOI: 10.1242/dmm.025247. View