Skip to main content

Expression of osteogenesis regulatory genes in the bone tissue of patients with acromegaly and endogenous hypercorticism

Abstract

Excessive hormone secretion during hypercorticism and acromegaly results in significant disturbances in bone remodeling, decrease in bone quality, and bone fractures following small traumas. However, the mechanisms of the development of such changes are not clear. In the present study, we examined specimens of bone tissue from patients with endogenous hypercorticism (increased cortisol secretion) and acromegaly (increased growth hormone secretion) obtained during transnasal adenomectomy. Our main purpose was to analyze the expression of genes responsible for osteogenesis in the bone tissue specimens from patients with hypercorticism and acromegaly, targeting an assessment of pathogenetic aspects associated with bone complications. The study included 19 specimens of bone tissue from patients with pituitary tumors (samples with acromegaly, Cushing disease, and inactive pituitary adenomas; the latter served as a control group). We revealed 14 genes (ACP5, ALPL, BGLAP, BMP7, CD40, COL1A1, COL1A2, IGF1, IGFBP2, IL6, LEP, LTA, MMP2, WNT10B) which appeared to be the most important and require further detailed study. The present study confirmed the key role of the Wnt-signaling pathway in the osteogenic process. In addition, we present new data on molecular mechanisms of development of skeletal complications in the case of cortisol and growth hormone oversecretion in humans.

This is a preview of subscription content, access via your institution.

References

  1. Dedov, I.I., Mel’nichenko, G.A., Belaya, Zh.E., et al., Osteoporosis—from a rare symptom of endocrine diseases to a silent epidemic of the 20—21 century, Probl. Endokrinol., 2011, vol. 57, no. 1, pp. 35–45.

    Article  Google Scholar 

  2. Grebennikova, T.A., Belaya, Zh.E., Rozhinskaya, L.Ya., et al., Epigenetic aspects of osteoporosis, Vestn. Ross. Akad. Med. Nauk, 2015, vol. 70, no. 5, pp. 541–548.

    Article  Google Scholar 

  3. Belaya, Zh.E., Didier, H., Rozhinskaya, L.Y., et al., The risk factors for fractures and trabecular bone-score value in patients with endogenous Cushing’s syndrome, Arch. Osteoporos., 2015, vol. 10, p. 44.

    Article  PubMed  Google Scholar 

  4. Belaya, Zh.E., Iljin, A.V., Melnichenko, G.A., et al., Diagnostic performance of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay in obese and overweight patients referred to exclude Cushing’s syndrome, Endocrine, 2012, vol. 41, no. 3, pp. 494–500.

    CAS  Article  PubMed  Google Scholar 

  5. Lekamwasam, S., Adachi, J.D., Agnusdei, D., et al., A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis, Osteoporos. Int. J. Establ. Result Coop. Eur. Found. Osteoporos. Natl. Osteoporos. Found. U.S.A., 2012, vol. 23, no. 9, pp. 2257–2276.

    CAS  Article  Google Scholar 

  6. Weinstein, R.S., Glucocorticoid-induced osteoporosis and osteonecrosis, Endocrinol. Metab. Clin. North Am., 2012, vol. 41, no. 3, pp. 595–611.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ohazama, A., Courtney, J.-M., and Sharpe, P.T., Opg,Rank,and Rankl in tooth development: co-ordination of odontogenesis and osteogenesis, J. Dent. Res., 2004, vol. 83, no. 3, pp. 241–244.

    CAS  Article  PubMed  Google Scholar 

  8. Kushlinskii, N.E., Timofeev, Yu.A., and Gershtein, E.S., The RANK/RANKL/OPG system for metastases and primary bone neoplasms, Mol. Med., 2013, no. 6, pp. 3–10.

    Google Scholar 

  9. Kuzma, M. and Payer, J., Growth hormone deficiency, its influence on bone mineral density and risk of osteoporotic fractures, Casopís Lékaru Ceských, 2010, vol. 149, no. 5, pp. 211–216.

    Google Scholar 

  10. Mazziotti, G., Biagioli, E., Maffezzoni, F., et al., Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis, J. Clin. Endocrinol. Metab., 2015, vol. 100, no. 2, pp. 384–394.

    CAS  Google Scholar 

  11. Watts, N.B., Bilezikian, J.P., Camacho, P.M., et al., American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis, Endocr. Pract. Off. J. Am. Coll. Endocrinol. Am. Ass. Clin. Endocrinol., 2010, vol. 16, suppl. 3, pp. 1–37.

    Google Scholar 

  12. Mel’nichenko, G.A., Dedov, I.I., Belaya, Zh.E., et al., The Itenko—Cushing disease: clinic, diagnostics, differential diagnosis, methods of treatment, Probl. Endokrinol., 2015, vol. 61, no. 2, pp. 55–77.

    Google Scholar 

  13. Dedov, I.I., Molitvoslovova, N.N., Rozhinskaya, L.Ya., et al., Federal clinical recommendations for clinic, diagnostics, differential diagnosis, and methods for the treatment of acromegaly, Probl. Endokrinol., 2013, vol. 59, no. 6, pp. 4–18.

    Google Scholar 

  14. Szklarczyk, D., Franceschini, A., Wyder, S., et al., STRING v10: protein—protein interaction networks, integrated over the tree of life, Nucleic Acids Res., 2015, vol. 43, pp. D447–D452.

    CAS  Article  PubMed  Google Scholar 

  15. Belaya, Zh.E., Rozhinskaya, L.Ya., Dragunova, N.V., et al., Metabolic complications of endogenous hypercorticism: selection of patients for screening, Ozhirenie Metab., 2013, no. 1, pp. 29–34.

    Google Scholar 

  16. Leclerc, N., Luppen, C.A., Ho Vincent, V., et al., Gene expression profiling of glucocorticoid-inhibited osteoblasts, J. Mol. Endocrinol., 2004, vol. 33, no. 1, pp. 175–193.

    CAS  Article  PubMed  Google Scholar 

  17. Rauch, A., Seitz, S., Baschant, U., et al., Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor, Cell Metab., 2010, vol. 11, no. 6, pp. 517–531.

    CAS  Article  PubMed  Google Scholar 

  18. Weinstein, R.S., Jilka, R.L., Parfitt, A.M., et al., Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of their deleterious effects on bone, J. Clin. Invest., 1998, vol. 102, no. 2, pp. 274–282.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Jia, D., O’Brien, C.A., Stewart, S.A., et al., Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density, Endocrinology, 2006, vol. 147, no. 12, pp. 5592–5599.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Weinstein, R.S., Chen, J.-R., Powers, C.C., et al., Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids, J. Clin. Invest., 2002, vol. 109, no. 8, pp. 1041–1048.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. I. Brovkina.

Additional information

Original Russian Text © O.I. Brovkina, Zh.E. Belaya, T.A. Grebennikova, D.S. Khodyrev, A.Ju. Grigoriev, P.M. Khandaeva, Ph.A. Koshkin, G.A. Melnichenko, A.G. Nikitin, 2017, published in Genetika, 2017, Vol. 53, No. 8, pp. 981–987.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Brovkina, O.I., Belaya, Z.E., Grebennikova, T.A. et al. Expression of osteogenesis regulatory genes in the bone tissue of patients with acromegaly and endogenous hypercorticism. Russ J Genet 53, 930–935 (2017). https://doi.org/10.1134/S102279541707002X

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S102279541707002X

Keywords

  • pituitary adenoma
  • osteogenesis
  • osteoporosis
  • osteoclasts
  • osteoblasts
  • expression
  • WNT