Cerulenin br Acknowledgments This work was supported

Acknowledgments This work was supported by grants from the National Science Council (project number: MOST-103-2320-B-040-004 and NSC 102-2313-B-002 -039 -MY3). The authors would like to thank Dr. Bernard A. Schwetz for carefully reading the manuscript and helpful discussions which improved the article quality. We also thank the Instrument Resource Center of Chung-Shan Medical University for the use of its chemiluminescence/fluorescence imaging analyzer.
Introduction Osteoporosis is a common public health problem affecting populations around the world. The typical characteristics of osteoporosis, such as low bone mineral density (BMD) and defects in the microarchitecture of bone tissue, result in an increase of bone fracture risk. The prevalence rate of osteoporosis increases as patients get older. In particular, there are many earlier studies demonstrating that the vital factor associated with an increased occurrence of osteoporosis in women aged 50 years is the extent of estrogen deficiency after menopause. Since estrogen regulates the balance between bone resorption and bone formation, hormone replacement therapy is believed to effectively treat postmenopausal osteoporosis. However, prolonged exposure to estrogen is associated with breast cancer, dysfunction of the vascular system, and serum lipid abnormality. While administration of the parathyroid hormone to osteoporotic patients induces bone formation by binding osteoblast lineage, its continuous treatment finally leads to bone loss due to downregulation of bone forming genes. In addition, the widely used antiresorptive drugs bisphosphonate and denosumab are reported to have serious side effects. For those reasons, it is important to develop a treatment for osteoporosis with appropriate efficacy without undesirable adverse effects. Lycii fructus, a dried mature fruit of Lycium chinense Mill (Solanaceae), has been traditionally used to treat musculoskeletal disorders based on classic Korean literature. In a previous report, Lycii radicis Cerulenin inhibited osteoclast differentiation in nuclear factor kappa-B ligand-induced RAW 264.7 cells. In addition, a herbal formula containing L. fructus exerted estrogenic activity in ovariectomized (OVX) rats. However, the ameliorative effect of L. fructus on osteoporosis has not yet been elucidated. In the present study, we aimed to analyze the bone mineral content (BMC) and BMD following L. fructus treatment in OVX-induced osteoporotic mice. In addition, histologic structure changes of bone were monitored along with serum osteocalcin and calcium concentrations.
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Discussion Finding effective treatment for osteoporosis is considered important because the fracture risk and difficulty of movement increases as bone strength weakens. Bone microstructure disruption and mechanical strength deterioration, result from a reduction in bone mass and BMD, and are hallmarks of osteoporosis. In particular, it is well-established that the assessment of BMC and BMD by dual-energy X-ray absorptiometry or microcomputed tomography are diagnostic criteria for osteoporosis. In this study, ovariectomy decreased the femoral BMC as well as BMD. The BMD of the distal femur in the LC-treated groups at 1 mg/kg and 100 mg/kg was much higher than that of the OVX group. The oral administration of LC also restored the femoral BMC levels. In conjunction with BMC and BMD, the histological change of bone structure was also observed. The hypertrophy of epiphyseal plate was markedly attenuated by LC treatment. We further evaluated the serum osteocalcin concentrations in each group to investigate the effects of LC on bone-turnover marker. Controlled remodeling between bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts) mainly occurs to maintain bone homeostasis. When osteoblasts form bone matrix consisting of collagen type I, osteopontin, and alkaline phosphatase, the process of bone growth or maturation of mineral phase is continued by secreting bone-turnover factors including osteocalcin and calcium. Therefore, osteocalcin and calcium are classic markers of osteoblastic maturation. A previous report indicates that serum osteocalcin is significantly decreased in OVX-induced osteoporotic mice. The treatment of LC increased the serum osteocalcin concentration. Additionally, the reduction of serum calcium in OVX mice was ameliorated by LC administration. Taken together, LC treatment increased not only serum osteocalcin, but also calcium concentration.