casticin and Osteoporosis

Osteoporosis has influenced millions of people, especially postmenopausal women, which has become a big burden to the whole world. Although the diverse roles of casticin (CAS) on different diseases were identified, whether it was implicated with osteoporosis was unknown.. A rat model of osteoporosis was established through dexamethasone (DEX) treatment and a cell model reflecting the osteogenic and osteoclast induction was constructed in bone marrow stromal cells (BMSCs). The calcification at the late stage of induction was measured via Alizarin Red S staining. Western blot was applied to evaluate the levels of proteins.. Hematoxylin and eosin staining revealed that the number of bone trabecular in DEX-induced osteoporosis rats was decreased, while increased doses of CAS treatment elevated the number of bone trabecular. CAS treatment alleviated DEX-induced osteoporosis in rats. Moreover, we found that CAS inhibited the nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) pathway. In addition, CAS promoted osteogenic differentiation of BMSCs and reduced osteoclastogenesis of bone marrow monocytes. Finally, CAS was observed to retard the receptor activator of NFκ-B ligand-induced NF-κB/MAPK pathway.. CAS promoted osteogenic differentiation of BMSCs and improved osteoporosis in rats by regulating the NF-κB/MAPK pathway. This might shed a light into using CAS as a drug treating osteoporosis in the future.

Topics: Animals; Cell Differentiation; Cells, Cultured; Female; Mesenchymal Stem Cells; Mitogen-Activated Protein Kinases; NF-kappa B; Osteogenesis; Osteoporosis; Rats

Postmenopausal osteoporosis is a systemic metabolic disease that chronically endangers public health and is typically characterized by low bone mineral density and marked bone fragility. The excessive bone resorption activity of osteoclasts is a major factor in the pathogenesis of osteoporosis; therefore, strategies aimed at inhibiting osteoclast activity may prevent bone decline and attenuate the process of osteoporosis. Casticin (Cas), a natural compound, has anti‑inflammatory and antitumor properties. However, the role of Cas in bone metabolism remains largely unclear. The present study found that the receptor activator of nuclear factor‑κΒ (NF‑κB) ligand‑induced osteoclast activation and differentiation were inhibited by Cas. Tartrate‑resistant acid phosphatase staining revealed that Cas inhibited osteoclast differentiation, and bone resorption pit assays demonstrated that Cas affected the function of osteoclasts. Cas significantly reduced the expression of osteoclast‑specific genes and related proteins, such as nuclear factor of activated T cells, cytoplasmic 1 and c‑Fos at the mRNA and protein level in a concentration‑dependent manner. Cas inhibited osteoclast formation by blocking the AKT/ERK and NF‑κB signaling pathways, according to the intracellular signaling analysis. The microcomputed tomography and tissue staining of tibiae from ovariectomized mice revealed that Cas prevented the bone loss induced by estrogen deficiency and reduced osteoclast activity in vivo. Collectively, these findings indicated that Cas may be used to prevent osteoporosis.

Topics: Animals; Bone Diseases, Metabolic; Bone Resorption; Cell Differentiation; Female; Humans; Mice; NF-kappa B; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Proto-Oncogene Proteins c-akt; RANK Ligand; Signal Transduction; X-Ray Microtomography