Abstract
Bone mineral density (BMD) and peak bone mass (PBM) are important determinants of skeletal resistance. The development of bone densitometry improved the possibility of studying BMD and the influence of genetic and environmental factors on bone. Heredity factors are important for BMD, and Runx-2 is accepted as a regulator of osteoblasts and bone formation. The aim of our study was to evaluate the behavior of Runx-2 during skeletal maturity in the healthy young-adult population. We analyzed spine and hip BMD in 153 volunteers, 98 women and 55 men, using dual-energy X-ray absorptiometry. In a subgroup of these volunteers, a sample of peripheral blood was taken to perform gene expression analysis of Runx-2 both in peripheral mesenchymal stem cells (MSCs; 28 subjects) and in peripheral mononuclear cells (PBMCs; 140 subjects). In our work BMD was comparable in both genders after puberty, then became higher in men than women during the third and fourth decades. PBM was achieved in the third decade in women and in the fourth in men. More interestingly, Runx-2 gene expression highly correlated with BMD in both genders. MSCs and PBMCs showed the same gene expression profile of Runx-2. In conclusion, PBM is reached earlier in females, BMD becomes higher in males later in life, and BMD and PBM are strictly associated with Runx-2. In addition, PBMC should be considered an important source for gene expression analysis in bone diseases.
Similar content being viewed by others
References
Bonjour JP, Theintz G, Buchs B, Slosman B, Rizzoli R (1991) Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J Clin Endocrinol Metab 73:555–563
Southard RN, Morris JD, Mahan JD, Hayes JR, Torch MA, Sommer A, Zipf WB (1991) Bone mass in healthy children: measurements with quantitative DXA. Radiology 179:735–738
Nguyen TV, Maynard LM, Towne B, Roche AF, Wisemandle W, Li J, Guo SS, Chumlea WC, Siervogel RM (2001) Sex differences in bone mass acquisition during growth. J Clin Densitom 4:147–157
Nelson DA, Simpson PM, Johnson CC, Barondness DA, Kleerekoper M (1997) The accumulation of whole body skeletal mass in third- and fourth-grade children: effects of age, gender, ethnicity and body composition. Bone Miner Res 20:73–78
Rosen CJ, Compston JE, Lian JB (2008) Childhood and adolescence. In: Rosen C (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 7th edn. American Society for Bone and Mineral Research. Lippincott Williams & Wilkins, New York, pp 72–98
Recker RR, Davies KM, Hinders SM, Heaney RP, Stegman MR, Kimmel DB (1992) Bone gain in young adult women. JAMA 268:2403–2408
Matkovic V, Jelic T, Wardlaw GM, Ilich JZ, Goel PK, Wright JK, Andon MB, Smith KT, Heaney RP (1994) Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. J Clin Invest 93:799–808
Christian JC, Yu PL, Slemenda CW, Johnston CC (1989) Heritability of bone mass: a longitudinal study in ageing male twins. Am J Hum Genet 44:429–433
Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC Jr (1991) Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 6:561–567
Seeman E, Hopper JL, Bach LA, Cooper ME, Parkinson E, McKay J, Jerums G (1989) Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 320:554–558
Evans RA, Marel GH, Lancaster EK, Kos S, Evans M, Wong YP (1988) Bone mass is low in relatives of osteoporotic patients. Ann Intern Med 109:870–873
Dalle Carbonare L, Valenti MT, Zanatta M, Donatelli L, Lo Cascio V (2009) Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis. Arthritis Rheum 60:3356–3365
Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754
Levanon D, Negreanu V, Bernstein Y, Bar-Am I, Avivi L, Groner Y (1994) AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics 23:425–432
Li YL, Xiao ZS (2007) Advances in Runx2 regulation and its isoforms. Med Hypotheses 68:169–175
Choi KY, Lee SW, Park MH, Bae YC, Shin HI, Nam S, Kim YJ, Kim HJ, Ryoo HM (2002) Spatiotemporal expression patterns of Runx2 isoforms in early skeletogenesis. Exp Mol Med 34:426–433
Ziros PG, Basdra EK, Papavassiliou AG (2008) Runx2: of bone and stretch. Int J Biochem Cell Biol 40:1659–1663
Ducy P, Starbuck M, Priemel M, Shen J, Pinero G, Geoffroy V, Amling M, Karsenty G (1999) Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev 13:1025–1036
Geoffroy V, Kneissel M, Fournier B, Boyde A, Matthias P (2002) High bone resorption in adult aging transgenic mice overexpressing cbfa1/runx2 in cells of the osteoblastic lineage. Mol Cell Biol 22:6222–6233
Maruyama Z, Yoshida CA, Furuichi T, Amizuka N, Ito M, Fukuyama R, Miyazaki T, Kitaura H, Nakamura K, Fujita T, Kanatani N, Moriishi T, Yamana K, Liu W, Kawaguchi H, Nakamura K, Komori T (2007) Runx-2 determines bone maturity and turnover rate on postnatal bone development and is involved in bone loss in estrogen deficiency. Dev Dyn 236:1876–1890
Melton LJ III, Khosla S, Atkinson EJ, O’Fallon WM, Riggs BL (1997) Relationship of bone turnover to bone density and fractures. J Bone Miner Res 12:1083–1091
Dalle Carbonare L, Valenti MT, Bertoldo F, Zanatta M, Zenari S, Realdi G, Lo Cascio V, Giannini S (2005) Bone microarchitecture evaluated by histomorphometry. Micron 36:609–616
Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765–771
Pineda B, Hermenegildo C, Laporta P, Tarin JJ, Cano A, Garcia-Perez MA (2010) Common polymorphisms rather than rare genetic variants of the Runx-2 gene are associated with femoral neck BMD in Spanish women. J Bone Miner Metab 28:696–705
Valenti MT, Dalle Carbonare L, Donatelli L, Bertoldo F, Zanatta M, Lo Cascio V (2008) Gene expression analysis in osteoblastic differentiation from peripheral blood mesenchymal stem cells. Bone (NY) 43:1084–1092
Heid CA, Stevens J, Livak KJ, Williams PM (1996) Real time quantitative PCR. Genome Res 6:986–994
Touchberry CD, Wacker MJ, Richmond SR, Whitman SA, Godard MP (2006) Age-related changes in relative expression of real-time PCR housekeeping genes in human skeletal muscle. J Biomol Tech 17:157–162
Radonic A, Thulke S, Mackay IM, Landt O, Siergert W, Nitsche A (2004) Guideline to reference gene selection for quantitative real-time PCR. Biochem Biophys Res Commun 313:856–862
Meijerink J, Mandigers C, Van de Locht L, Tonnissen E, Goodsaid F, Raemaekers J (2001) A novel method to compensate for different amplification efficiencies between patient DNA samples in quantitative real-time PCR. J Mol Diagn 3:55–61
Falconi D, Oizumi K, Aubin JE (2007) Leukemia inhibitory factor influences the fate choice of mesenchymal progenitor cells. Stem Cells 25:305–312
Liew CC (2006) The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J Lab Clin Med 147:126–132
Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 11(suppl 6):S2–S17
Fatayerji D, Eastell R (1999) Age-related changes in bone turnover in men. J Bone Miner Res 14:1203–1210
Hsiao LL, Dangond F, Yoshida T, Hong R, Jensen RV et al (2001) A compendium of gene expression in normal human tissues. Physiol Genomics 7:97–104
Zhong H, Simons JW (1999) Direct comparison of GAPDH, beta-actin, cyclophilin, and 28S rRNA as internal standards for quantifying RNA levels under hypoxia. Biochem Biophys Res Commun 259:523–526
Jemiolo B, Trappe S (2004) Single muscle fiber gene expression in human skeletal muscle: validation of internal control with exercise. Biochem Biophys Res Commun 320:1043–1050
Valenti MT, Bertoldo F, Dalle Carbonare L, Azzarello G, Zenari S, Zanatta M, Balducci E, Vinante E, Lo Cascio V (2006) The effect of bisphosphonates on gene expression: GAPDH as a housekeeping or a new target gene? BMC Cancer 6:49–55
Conflict of interest
None of the authors has any conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Zanatta, M., Valenti, M.T., Donatelli, L. et al. Runx-2 gene expression is associated with age-related changes of bone mineral density in the healthy young-adult population. J Bone Miner Metab 30, 706–714 (2012). https://doi.org/10.1007/s00774-012-0373-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00774-012-0373-1