Obesity and osteoporosis are two prevalent conditions
that are
becoming increasingly common worldwide, primarily due to aging populations,
imbalanced energy intake, and sedentary lifestyles. Obesity, characterized
by excessive fat accumulation, and osteoporosis, marked by reduced
bone density and increased fracture risk, are often interconnected.
High-fat diets (HFDs) can exacerbate both conditions by promoting
bone marrow adiposity and bone loss. The effect of WFA on the osteogenesis
and adipogenesis was studied on the C3H10T1/2 cell line and bone marrow
mesenchymal stem cells (BM-MSCs) isolated from mice. We used oil red
O and alkaline phosphatase (ALP) staining to observe adipogenesis
and osteogenesis, respectively, in MSCs. Real-time PCR and Western
blot analyses were used to study the molecular effects of WFA on MSCs.
We employed micro-CT to analyze the bone microarchitecture, bone mineral
density (BMD), and abdominal fat mass in male mice. We have used osmium
tetroxide (OsO4) staining to study the bone marrow fat.
WFA induced the C3H10T1/2 cell line and BM-MSCs toward osteogenic
lineage as evidenced by the higher ALP activity. WFA also downregulated
the lipid droplet formation and adipocyte specific genes in MSCs.
In the in vivo study, WFA also suppressed the bone
catabolic effects of the HFD and maintained the bone microarchitecture
and BMD in WFA-treated animals. The bone marrow adipose tissue was
reduced in the tibia of WFA-treated groups in comparison with only
HFD-fed animals. Withaferin A was able to improve the bone microarchitecture
and BMD by committing BM-MSCs toward osteogenic differentiation and
reducing marrow adiposity. The findings of this study could provide
valuable insights into the therapeutic potential of Withaferin A for
combating bone marrow obesity and osteoporosis, particularly in the
context of diet-induced metabolic disturbances.
