MiR­519d­3p ГАЛЬМУЄ ОСТЕОКЛАСТОГЕНЕЗ ЧЕРЕЗ ЗНИЖЕННЯ ЕКСПРЕСІЇ MMP2 ТА ЗСУВ СИГНАЛІНГУ В ОСТЕОБЛАСТАХ У БІК ЕКСПРЕСІЇ ОСТЕОПРОТЕГЕРИНУ

• Date: 2026
• Main Authors: Sun, Bo, Huang, Tao, He, Xianbo, Wang, Wenbo, Tang, Sanquan, Tian, Wenlin
• Format: Article
• Language: English
• Published: PH Akademperiodyka 2026
• Subjects: miR-519d-3p; MMP-2; остеокластогенез; остеобласт; кондиційоване середовище; тартрат-резистентна кисла фосфатаза
• Online Access: https://exp-oncology.com.ua/index.php/Exp/article/view/582
• Journal Title: Experimental Oncology

Background. Paracrine crosstalk between tumor cells and bone-resident cells drives osteoclastogenesis in the metastatic bone niche. miR-519d-3p has been linked to suppression of matrix metalloproteinases. Aim. To test whether osteoblastic miR-519d-3p restrains tumor-conditioned osteoclastogenesis by lowering MMP2 expression and shifting signaling toward osteoprotegerin (OPG). Materials and Methods. Mouse osteoblasts (MC3T3-E1) were transfected with miR‑519d-3p mimic, inhibitor, or corresponding negative controls. Osteoblast-conditioned medium (OB-CM) was mixed 1:1 with MDA-MB-231 tumor-conditioned medium (231-CM) and applied to bone-marrow-derived macrophages for tartrate-resistant acid phosphatase (TRAP) staining. Osteoblastic MMP2 and OPG mRNAs were quantified by RT-qPCR, and a dual-luciferase system compared the wild-type vs seed-mutant MMP2 3′UTR reporters. Results. Relative to their controls, miR-519d-3p mimic OB-CM produced fewer TRAP-positive multinucleated osteoclasts, whereas inhibitor OB-CM produced more. In osteoblasts, the mimic decreased MMP2 mRNA, whereas the inhibitor increased it, and the changes in OPG mRNA were modest. Dual-luciferase assays did not show a reproducible wildtype–over-mutant selective repression by miR-519d-3p, indicating context-dependent or indirect regulation of MMP2. Conclusion. Elevating osteoblastic miR-519d-3p in vitro associated with lower MMP2 and an anti-osteoclastogenic paracrine output, suggesting a tractable microRNA-based approach to modulate the metastatic bone niche and warranting further validation in vivo.