Abstract
BackgroundDysfunctional osteogenesis of bone marrow mesenchymal stem cells (BMSCs) plays an important role in osteoporosis occurrence and development. However, the molecular mechanisms of osteogenic differentiation remain unclear. This study explored whether microfibrillar-associated protein 5 (MFAP5) regulated BMSCs osteogenic differentiation.MethodsWe used shRNA or cDNA to knock down or overexpress MFAP5 in C3H10 and MC3T3-E1 cells. AR-S- and ALP-staining were performed to quantify cellular osteogenic differentiation. The mRNA levels of the classical osteogenic differentiation biomarkers Runx2, Col1α1, and OCN were quantified by qRT-PCR. Finally, we employed Western blotting to measure the levels of Wnt/β-catenin and AMPK signaling proteins.ResultsAt days 0, 3, 7, and 14 after osteogenic induction, AR-S- and ALP-staining was lighter in MFAP5 knockdown compared to control cells, as were the levels of Runx2, Col1α1 and OCN. During osteogenesis, the levels of β-catenin, p-GSK-3β, AMPK, and p-AMPK were upregulated, while that of GSK-3β was downregulated, indicating that Wnt/β-catenin and AMPK signaling were activated. The relevant molecules were expressed at lower levels in the knockdown than control group; the opposite was seen for overexpressing cell lines.ConclusionsMFAP5 regulates osteogenesis via Wnt/β‑catenin- and AMPK-signaling; MFAP5 may serve as a therapeutic target in patients with osteoporosis.
Highlights
Dysfunctional osteogenesis of bone marrow mesenchymal stem cells (BMSCs) plays an important role in osteoporosis occurrence and development
Metformin could directly contribute to osteogenesis by activating AMPK and expression of Runt-related transcription factor 2 (Runx2) (Molinuevo et al 2010). All these findings suggested the crucial function of Wnt/β-catenin and AMPK pathways in regulating BMSCs osteogenesis
microfibrillar-associated protein 5 (MFAP5) expression correlated positively with osteogenesis To explore the potential role played by MFAP5 in osteogenesis, we analyzed the GSE156508 database, which includes data on the primary osteoblasts of women with osteoporotic fractures (n = 6) and severe osteoarthritis (n = 6)
Summary
Dysfunctional osteogenesis of bone marrow mesenchymal stem cells (BMSCs) plays an important role in osteoporosis occurrence and development. The molecular mechanisms of osteogenic differentiation remain unclear. This study explored whether microfibrillar-associated protein 5 (MFAP5) regulated BMSCs osteogenic differentiation. Osteoporosis is very common worldwide, and is associated with bone fragility caused by osteopenia, reduced bone mass, and an increased fracture risk (Coughlan and Dockery 2014; Kanis 1994; Wang et al 2009). It is accepted that reduced proliferation and osteogenesis of bone marrow mesenchymal stem cells (BMSCs) are closely associated with osteoporosis occurrence and progression (Liu et al 2021; Luo. Li et al Molecular Medicine (2021) 27:153 et al 2019). Due to the unclear mechanism of osteogenic differentiation, few methods could be applied to treat osteoporosis in clinical by targeting osteoblastic cells. More effective genes that could regulating osteogenesis need to be identified which could provide potential targets and develop drugs for patients suffering from osteoporosis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
