Effects of active acromegaly on bone mRNA and microRNA expression patterns

Belaya, Zhanna; Grebennikova, T. A.; Melnichenko, Galina; Nikitin, Alexey; Solodovnikov, Alexander; Brovkina, Olga; Grigoriev, Andrey; Rozhinskaya, Ludmila; Lutsenko, Alexander; Дедов, И И

doi:10.1530/eje-17-0772

Cited by 22 publications

(15 citation statements)

References 51 publications

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“…The increased bone remodeling is likely due to the actions of IGF-I on the induction of RANKL leading to enhanced osteoclastogenesis (40,72,73). Analyzing gene expression in sphenoid bone tissue samples of subjects with acromegaly, Belaya et al suggested that GH excess may induce mesenchymal stem cell commitment toward cartilage or adipocytes instead of toward mature osteoblasts (74). It was hypothesized that the cartilage growth induced by GH excess may influence osteoblast and osteoclast function directly in a way similar to the one occurring during normal endochondral ossification (74).…”

Section: Effects Of Gh Excess On Bone Formation and Resorptionmentioning

confidence: 99%

“…Analyzing gene expression in sphenoid bone tissue samples of subjects with acromegaly, Belaya et al suggested that GH excess may induce mesenchymal stem cell commitment toward cartilage or adipocytes instead of toward mature osteoblasts (74). It was hypothesized that the cartilage growth induced by GH excess may influence osteoblast and osteoclast function directly in a way similar to the one occurring during normal endochondral ossification (74). One may speculate that acromegalic osteopathy and arthropathy share common pathophsyiological mechanisms ( Fig.…”

Section: Effects Of Gh Excess On Bone Formation and Resorptionmentioning

confidence: 99%

“…However, it is unclear whether the decrease in bone turnover is accompanied by an improvement in bone structure, and a reduction in fracture risk. Recent studies hypothesized that osteoblastogenesis may be impaired in subjects with controlled acromegaly, but the studies do not offer a direct proof that osteoblast number or function is altered in these individuals (74,106,107). Dalle Carbonare et al reported decreased osteoblast number and function and reduced osteocyte number in bone samples from patients with controlled acromegaly compared to those with active disease, but the impact of these histomorphometric findings on fracture risk was uncertain since all subjects included in the study had VFs (81).…”

Section: Effects Of Acromegaly Therapy On Bone Turnover Bone Structumentioning

confidence: 99%

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MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment

Mazziotti

Lania

Canalis

2019

European Journal of Endocrinology

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Growth hormone (GH) and insulin-like growth factor-I (IGF-I) exert physiological actions on the skeleton throughout life, by stimulating longitudinal bone growth in children, the acquisition of bone mass during adolescence and the maintenance of skeletal architecture in adults. When GH and IGF-I are secreted in excess, bone remodeling is enhanced leading to deterioration of bone microstructure and impairment of bone strength. Indeed, acromegaly causes skeletal fragility, and vertebral fractures are reported in a remarkable number of subjects exposed to GH and IGF-I excess. The management of skeletal fragility in acromegaly is a challenge, since the awareness of this complication is low, the prediction of fracture risk is difficult to ascertain, the risk of fractures remains after the control of acromegaly and the effectiveness of bone-active drugs is unknown. This review is an update on bone disorders associated with acromegaly and provides a perspective of possible therapeutic approaches based on emerging pathophysiological and clinical information.

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Section: Effects Of Gh Excess On Bone Formation and Resorptionmentioning

confidence: 99%

Section: Effects Of Gh Excess On Bone Formation and Resorptionmentioning

confidence: 99%

Section: Effects Of Acromegaly Therapy On Bone Turnover Bone Structumentioning

confidence: 99%

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MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment

Mazziotti

Lania

Canalis

2019

European Journal of Endocrinology

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“…In mesenchymal progenitor cells, chondrogenic and osteo-genic cell lines, it has also been identified that miR-204 is able to bind to the 3′-UTR of the Runx2 gene and regulate its expression ( 12 , 13 ). Another study identified that, among the genes involved in osteoblast and osteoclast activity, changes in miRNAs are involved in osteoblastogenesis, including miR-204-5p, but Runx2 was unchanged in patients with clinically and biochemically confirmed acromegaly ( 14 ). However, to the best of our knowledge, no previous study has investigated the potential function of miR-204-5p and its association with Runx2 in OA.…”

Section: Introductionmentioning

confidence: 99%

miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2

Cao

Han

et al. 2018

Int J Mol Med

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One of the hallmarks of osteoarthritis (OA) development is endochondral ossification, in which Runt-related transcription factor-2 (Runx2) is aberrantly expressed. Runx2 was previously identified to be regulated by microRNA-204-5p (miR-204-5p). The aim of the present study was to investigate the potential function of miR-204-5p regulating Runx2 during the development of OA and the underlying molecular mechanism. The expression levels of miR-204-5p and Runx2 were determined in tissue specimens. Rat OA models were established by transecting the anterior and posterior cruciate ligaments and removing the meniscus. Rats were treated with miR-204-5p agomir and miR-204-5p negative control (NC). All in vitro experiments were performed using rat primary chondrocytes and the SW-1353 human bone chondrosarcoma cell line. It was identified that the expression of miR-204-5p was significantly decreased, whereas Runx2 was significantly increased, in human OA tissues compared with in non-OA tissues, and levels were inversely associated with each other in primary chondrocytes and chondrosarcoma cells. Overexpression of miR-204-5p decreased the proliferation of chondrocytes and SW-1353 cells. Using a luciferase reporter assay, Runx2 was identified to be a direct target of miR-204-5p in chondrocytes and overexpressed miR-204-5p altered the expression of collagens II, X and matrix metalloproteinase (MMP)-1 and MMP-13 in primary chondrocytes and SW-1353 cells. Histological analysis revealed that miR-204-5p treatment ameliorated the OA-like phenotype that is reflected by assessment of cartilage thickness and Mankin's score. Runx2 expression was gradually increased as the rats increased in age. At 10 weeks of miR-204-5p agomir treatment, altered expression levels of collagens II and X, cartilage oligomeric matrix protein fragment, aggrecan, MMP-1 and MMP-13 were observed in the treatment group compared with the NC group. In conclusion, the results of the present study indicated that miR-204-5p decreases chondrocyte proliferation and ameliorates the OA-like phenotype in rats with surgically induced OA by targeting Runx2.

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“…miRNA-211 has a well-established role in various pathologies (12–14) and plays a major role in melanoma development (15–18) and in development of other types of cancer including leukemia (19), glioblastoma (20), and breast cancer (21). In Burkitt’s lymphoma, a Myc-driven tumor, Bmal1 / Clock and miRNA-211 expression patterns are inversely correlated.…”

mentioning

confidence: 99%