Effects of endogenous hypercortisolism on bone mRNA and microRNA expression in humans

• Published in: Osteoporosis international 2018, Vol.29 (1), p.211-221
• Main Authors: Belaya, Z. E., Grebennikova, T. A., Melnichenko, G. A., Nikitin, A. G., Solodovnikov, A. G., Brovkina, O. I., Grigoriev, A. U., Rozhinskaya, L. Y., Dedov, I. I.
• Format: Article
• Language: English
• Subjects: Adipocytes; Adrenocorticotropic hormone; Adult; Antagonists; Body mass index; Bone Density - genetics; Bone Density - physiology; Bone growth; Bone morphogenetic protein 2; Bone remodeling; Bone Remodeling - genetics; Bone Remodeling - physiology; Cartilage; Cbfa-1 protein; Cell culture; Cell Differentiation - genetics; Chromosome 5; Collagen (type I); Cushing syndrome; Cushing's disease; Dkk1 protein; Endocrinology; Female; Gene expression; Gene Expression Regulation - physiology; Glucocorticoids; Humans; LRP5 protein; Male; Medicine; Medicine & Public Health; Mesenchyme; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; mRNA; Nervous system diseases; Original Article; Orthopedics; Osteoblastogenesis; Osteoblasts - pathology; Osteoclastogenesis; Osteoclasts - physiology; Osteogenesis; Osteoporosis; Osteoporosis - etiology; Osteoporosis - genetics; Osteoporosis - pathology; Osteoporosis - physiopathology; Pituitary; Pituitary ACTH Hypersecretion - complications; Pituitary ACTH Hypersecretion - genetics; Pituitary ACTH Hypersecretion - metabolism; Pituitary ACTH Hypersecretion - pathology; Rheumatology; RNA, Messenger - genetics; Sphenoid Bone - metabolism; Sphenoid Bone - pathology; Stem cells; Wnt Signaling Pathway - genetics; Wnt Signaling Pathway - physiology
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-017-4241-7

Summary Hypercortisolism in humans suppresses osteoblastogenesis and osteoblast function through the upregulation of Wnt-signaling antagonists (sclerostin, Dkk1) and changes in microRNAs levels (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) which are associated with mesenchymal stem-cell commitment to adipocytes or cartilage cells over the osteoblasts. Introduction The purpose of this study was to evaluate the responses of bone to chronic glucocorticoid (GC) excess by measuring the levels of selected mRNA and microRNA (miR) in bone samples of patients with Cushing’s disease (CD). Methods Bone samples were obtained during transsphenoidal adenomectomy from the sphenoid bone (sella turcica) from 16 patients with clinically and biochemically evident CD and 10 patients with clinically non-functioning pituitary adenomas (NFPA) matched by sex, age, and body mass index. Quantitative polymerase chain reactions (qPCR) were used to examine the expression of genes (mRNA and miRs) known to be involved in bone remodeling regulation based on studies in animals and cell culture. Results Hypercortisolism was associated with the downregulation of genes involved in osteoblast function and maturation (ACP5, ALPL, BGLAP, COL1A1, COL1A2, BMP2, RUNX2, TWIST1). An excess of GC caused increased expression of Wnt-signaling antagonists (Dkk1, SOST) and changes in the levels of miRs that are known to suppress osteoblastogenesis (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) p