ISSN ONLINE: 2558-815X
ISSN PRINT: 1584-9244
ISSN-L: 1584-9244

The role of sclerostin and PGC-1 alpha in the pathogenesis of osteoporosis



Introduction. Canonical Wnt signaling pathway regulates stromal stem cells (SSCs) differentiation and controls the balance between adipogenesis and osteogenesis. Estrogen deficiency affects Wnt signaling by altering the expression of sclerostin (SCL) and the peroxisome proliferator-activated receptor-∝ coactivator 1-∝(PGC-1∝) in the bone tissue.

The objective of the study was to monitor whether there is a feedback mechanism between SCL and PGC-1∝ and to determine the extent of the immunohistochemical staining of PGC-1∝ and SCL in bone tissue of estrogen deficiency-induced osteoporosis in female Wistar rats.

Materials and methods. An experiment was performed on 20 female Wistar rats at reproductive age (2 months), divided into 2 groups: in group 1 (G1) 10 animals were ovariectomized (ovx) and in group 2 (G2) 10 of the remaining were sham-operated (sham).

Results. We found that the PGC-1∝ in the bone marrow stromal cells was reduced in the group with osteoporosis (G1 – ovariectomized rats), compared to sham-operated control group G2 (p<0.05). The SCL in osteocytes was increased in the group with osteoporosis – G1, compared to control group G2 (p<0.05). Histomorphological analysis of femur from G1 animals indicated reduced areas of mineralized tissue and bone marrow fatty degeneration.

Conclusions. Estrogen deficiency in G1 ovx rats increased the expression of SCL in the osteocytes by activating osteoclastic bone resorption and reduced PGC-1∝ expression in SSCs cells, which stimulated adipogenic differentiation that led to significant fatty degeneration in the bone marrow. We confirmed the exceptional role of PGC-1a and SCL in the pathogenesis of osteoporosis and that there is a mechanism of feedback loop between SCL and PGC-1∝.

Keywords: PGC-1∝, sclerostin, estrogen deficiency, osteoporosis.

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Address for correspondence:
Department of „Physiology and Pathophysiology“, Medical University-Pleven, Bulgaria
Address: St. Kliment Ohridski, 5800 Pleven, Bulgaria


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Grigoryan AV, Betova TM, Dineva TB, Popovska SL, Trifonov RG, Dimitrova AA. The role of sclerostin and PGC-1 alpha in the pathogenesis of osteoporosis. Arch Balk Med Union. 2020;55(2):284-289.