Impact of Polyrhodanine Manganese Ferrite Binary Nanohybrids (PRHD@MnFe2O4) on Osteoblasts and Osteoclasts Activities—A Key Factor in Osteoporosis Treatment

Abstract

Osteoporosis is characterized by the reduction of bone mineral density and the weakness of the bone strength leading to fractures. Searching for new compounds that stimulate bone activity and their ability to reconstruct seems to be a promising tool in osteoporosis treatment. Here, we performed analyses comparing the impact of polyrhodanine (PRHD) and its derivatives on the viability (anti-proliferative tests), morphology and mitochondrial network (confocal microscopy) towards pre-osteoblasts (MC3T3-E1 cell line) and osteoclasts (4B12 cell line). Moreover, we assessed the expression of genes associated with the apoptosis, inflammation and osteogenic differentiation by qPCR technique. Our results clearly demonstrated that PRHD and its modification at ratio 10/90 significantly improves the pre-osteoblast’s proliferative abilities, while reducing osteoclast function. The observed effects were strongly correlated with the cytoskeleton and mitochondrial network development and arrangement. Additionally, the expression profile of genes revealed enhanced apoptosis of osteoclasts in the case of PRHD and its modification at ratio 10/90. Moreover, in this case we also observed strong anti-inflammatory properties demonstrated by decreased expression of Il1b, Tnfa and Tgfb in pre-osteoblasts and osteoclasts. On the other hand, enhanced expression of the markers associated with bone remodeling, namely, osteopontin (OPN), osteocalcin (OCL) and alkaline phosphatase (ALP), seem to confirm the role of PRHD@MnFe2O4 in the promotion of differentiation of pre-osteoblasts through the ALP-OPN-OCL axis. Based on these observations, PRHD@MnFe2O4 could be a potential agent in osteoporosis treatment in future, however, further studies are still required.

Prognostic analysis and validation of diagnostic marker genes in patients with osteoporosis

“…RT-qPCR results showed significant differences in the MAPK signaling pathway (p38, TRAF6) and NF-kappaB signaling pathway (c-FLIP, MIP1β). Previous studies have shown that OPG/RANK/RANKL ( 9 ), IL-1β ( 47 ),TRAF6 ( 48 ), NFATc1, OSCAR and NF-κB ( 49 ), and other genes related to apoptosis, inflammation, and osteogenic differentiation ( 6 ). These genes regulate bone metabolism via the MAPK signaling pathway and TNF signaling pathway, which affects OP.…”

“…Bone homeostasis depends on osteoclast resorption and osteoblast formation, and an imbalance in this tightly coupled process can lead to the development of osteoporosis ( 5 ). Hip and vertebral fractures are two common osteoporotic fractures ( 6 ). Elderly patients with osteoporotic fractures often require hospitalization, resulting in poor quality of life, long-term medical care, disability, and even death ( 7 ).…”