crocin and Osteoporosis

Osteoblast apoptosis has been identified as an important event in the development of glucocorticoid (GC)‑induced osteoporosis and osteonecrosis of the femoral head. Crocin, a bioactive ingredient of saffron, has been demonstrated to induce antiapoptotic effects on numerous types of cell in vitro; however, the effects of crocin on the dexamethasone (Dex)‑induced apoptosis of osteoblasts remain unclear. In the present study, the protective effects of crocin during Dex‑induced apoptosis of MC3T3‑E1 osteoblasts, and the underlying mechanisms, were investigated. MTT and Annexin V‑FITC/PI flow cytometry assays were performed to evaluate the viability and apoptosis of cells, respectively. The mitochondrial transmembrane potential, reactive oxygen species (ROS), intracellular Ca2+ levels and apoptosis‑associated protein expression were assessed via flow cytometry, fluorescence microscopy and western blotting. It was demonstrated that crocin pretreatment inhibited Dex‑induced apoptosis of osteoblasts in a dose‑dependent manner. Crocin reversed Dex‑induced decreases in the mitochondrial transmembrane potential, and increases in ROS and intracellular Ca2+ levels. Furthermore, crocin upregulated the expression levels of B‑cell lymphoma-2 (Bcl‑2) and mitochondrial cytochrome c (Cyt C), and downregulated those of cleaved caspase‑9, cleaved caspase‑3, Bcl‑2‑associated X protein and cytoplasmic Cyt C. N‑acetylcysteine, a ROS inhibitor, and 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid, a calcium chelator, attenuated Dex‑induced osteoblast apoptosis, whereas H2O2 and ionomycin, a calcium ionophore that increases intracellular calcium levels, reversed the antiapoptotic effects of crocin on Dex‑treated osteoblasts. These results indicated that crocin may protect osteoblasts from Dex‑induced apoptosis by inhibiting the ROS/Ca2+‑mediated mitochondrial pathway, thus suggesting that crocin has potential value as a treatment for GC‑induced bone diseases.

Topics: Acetylcysteine; Animals; Apoptosis; Calcium; Carotenoids; Cell Survival; Dexamethasone; Femoral Fractures; Glucocorticoids; Humans; Hydrogen Peroxide; Ionomycin; Membrane Potential, Mitochondrial; Mice; Mitochondria; Osteoblasts; Osteonecrosis; Osteoporosis; Reactive Oxygen Species; Signal Transduction

In the current study, anti-osteoporotic activities of crocin were evaluated in a rat model of metabolic syndrome-induced osteoporosis. Metabolic syndrome was confirmed by increased body weight gain, increased fasting blood glucose, hyperinsulinemia, elevated mean arterial blood pressure, and increased serum triglycerides level. Crocin (5 or 10 mg/kg) protected against histological and architectural alteration in bone tissues. Further, it ameliorated the decline in the bone formation markers serum alkaline phosphatase activity and osteocalcin level and inhibited the rise in the bone resorption markers serum tartrate-resistant acid phosphatase and collagen cross-linking carboxyterminal telopeptide, type I. Crocin anti-inflammatory properties were confirmed by a significant decline in serum interleukin-6 and tumor necrosis factor-α. Crocin mitigated oxidative stress in femur distal epiphysis tissues. Mechanically, crocin enhanced both the longitudinal and perpendicular forces of femurs. The current data highlight a protective activity that can be attributed, at least partly, to its anti-inflammatory and antioxidant activities. PRACTICAL APPLICATIONS: Metabolic syndrome is a serious health problem. Its prevalence is present in approximately 25% of all adults. Complications of metabolic syndrome include osteoporosis. This poses high risk of fractures and represents a heavy health, social, and economic burden. The current study highlights the antiosteoporotic activities of crocin in an experimental model of osteoporosis. Thus, crocin and/or other structurally related carotenoids can be lead compounds for synthesizing more potent and bioavailable molecules. These are expected to be devoid of the hazardous adverse effects of the currently available medicaments.

Topics: Animals; Anti-Inflammatory Agents; Carotenoids; Female; Interleukin-6; Metabolic Syndrome; Osteoporosis; Oxidative Stress; Rats; Tumor Necrosis Factor-alpha