Ethyl Acetate Fraction from Cudrania Tricuspidata Inhibits IL-1beta-Stimulated Osteoclast Differentiation through Downregulation of MAPKs, c-Fos and NFATc1

BACKGROUND/AIMS: The present study was performed to determine the effects of the ethyl acetate extract of Cudrania tricuspidata (EACT) on interleukin (IL)-1beta-stimulated receptor activator of NF-kappaB ligand (RANKL)-mediated osteoclast differentiation. METHODS: Bone marrow cells were harvested from 6-week-old male imprinting control region mice, and the differentiation of osteoclasts from these cells was evaluated by tartrate-resistant acid phosphatase and resorption pit formation assay. Phosphorylated extracellular signal regulated kinase (p-ERK), phosphorylated p38, phosphorylated c-Jun amino-terminal kinase, NF-kappaB (p65), IkappaBalpha, c-Fos, and nuclear factor of activated T-cells c1 (NFATc1) expression was examined by immunoblotting and quantitative reverse transcription-polymerase chain reaction. RESULTS: EACT inhibits IL-1beta-stimulated RANKL-mediated osteoclast differentiation. EACT also inhibits IL-1beta-stimulated RANKL-mediated phosphorylation of ERK 1/2, p38 mitogen activated protein kinase, and expression of c-Fos and NFATc1. CONCLUSIONS: These results suggest that EACT may be involved in the inhibition of bone loss by preventing osteoclast formation and may be used to manage bone destruction in inflammatory diseases, such as rheumatoid arthritis.

The Impact of Apolipoprotein E Genetic Polymorphism on Bone Mineral Density in Postmenopausal Women with Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: To evaluate the relationship between the presence of apolipoprotein E (Apo E) 4 allele and bone mineral density (BMD) and severity of joint destruction in postmenopausal women with rheumatoid arthritis (RA). METHODS: Apo E genotypes were analyzed in 113 postmenopausal women who were first diagnosed with RA and had not receiving antiresorptive therapy for osteoporosis at the time of enrollment. BMD was measured using dual-energy X-ray absorptiometry (DEXA), and joint destruction was evaluated on plain radiographs according to 'Larsen score'. The differences in BMD and severity of joint destruction in groups with and without an Apo E4 allele were analyzed in 94 patients with clinical information available. RESULTS: BMD (g/cm2) of the lumbar spine in the Apo E4 (-) group was 0.94+/-0.16 (n=67), whereas that in the Apo E4 (+) group was 0.87+/-0.14 (n=27; p=0.049). BMD of the femoral neck and great trochanter in the Apo E4 (-) group was 0.74+/-0.12 and 0.63+/-0.11, while that in the Apo E4 (+) group was 0.68+/-0.11 (p=0.039) and 0.57+/-0.11 (p=0.008). However, there were no significant differences in Larsen scores and erosive disease (%) between the Apo E4 (+) and Apo E4 (-) groups. CONCLUSION: The Apo E4 allele is associated with a reduced bone mass in postmenopausal RA patients. Therefore, Apo E4 allele is considered to be an independent risk factor for generalized osteoporosis in postmenopausal RA patients.