Benzofuran pyran hybrid prevents glucocorticoid induced osteoporosis in mice via modulation of canonical Wnt/β-catenin signaling

Abstract

Glucocorticoid induced osteoporosis (GIOP) is the second most leading cause of osteoporosis. We have identified a compound, a benzofuran pyran hybrid compound 4e that has osteogenic potential and we wanted to assess its efficacy in GIOP in male mice. We assessed the effect of dexamethasone and compound 4e on primary osteoblasts using various cell based and immunofluorescence assays. For in vivo studies we administered methylprednisolone and compound 4e as a prophylactic measure in male Balb/c mice for 28 days and then evaluated the effect on bone microarchitecture by microCT, bone formation by histology along with clinically relevant bone markers. Compound 4e preserved osteoblast differentiation as evident by higher ALP positive cells and mineralization in compound treated groups. Compound 4e also increased the expression of osteogenic genes. This compound guarded β-catenin expression both in vitro and in vivo as confirmed by western blot and immunofluorescence assays. This led to the preservation of bone microarchitecture and cortical thickness at 2.5 mg kg −1 and 5 mg kg −1 doses. Further compound 4e enhanced bone formation rate and regulated osteocyte death. The osteogenic potential of compound 4e was reflected by an increased level of serum marker osteocalcin and decreased levels of SOST and CTX-I. Overall, Compound 4e is able to overcome the catabolic effect of dexamethasone on bone by targeting the canonical WNT/β-catenin signaling as evidenced by both in vitro and in vivo studies.

Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress

“…Accordingly, our results revealed that DEX downregulated Wnt and osteocalcin mRNA expression, along with the protein expression of p-Akt in femur bone tissues. The obtained results are in line with earlier studies [15,21,[51][52][53]. Furthermore, we are first to demonstrate that these effects were greatly reversed by combining DEX with diosmin.…”

Alpinetin alleviates osteoporosis by promoting osteogenic differentiation in BMSCs by triggering autophagy via PKA/mTOR/ULK1 signaling

“…Osteoporosis will decrease the BV/TV, trabecular number, trabecular thickness, and increase trabecular spacing. In addition, analysis of cortical bone is an important indicator of pure anabolic effect in the process of osteoporosis (Song et al, 2020 ; Tripathi et al, 2022 ). Therefore, we tested these indicators in the GIOP mouse model.…”

Vitamin D(3) and methylenebisphosphonic acid in the correction of mineral metabolism disorders and bone remodeling associated with glucocorticoid-induced osteoporosis

“…The adipogenic differentiation of bone marrow mesenchymal stem cells is facilitated by an increased expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), thus leading to fat accumulation in the bone marrow and to bone loss in patients chronically supplemented with glucocorticoids. It is noteworthy that Wnt/β-catenin signaling pathway-activating compounds can prevent the development of GIOP [9], including vitamin D 3 (VD 3 ).…”