Amiloride inhibits osteoclastogenesis by suppressing nuclear factor-κB and mitogen-activated protein kinase activity in receptor activator of nuclear factor-κB-induced RAW264.7 cells.

Amiloride is widely used in clinical practice as a diuretic and is known to interact with the epithelial sodium channel and acid­sensing ion channel proteins, as well as Na+/H+ antiporters and Na+/Ca2+ exchangers. The aim of the present study was to examine the effects of amiloride on receptor activator of nuclear factor­κB ligand (RANKL)­induced osteoclastogenesis and to elucidate the underlying mechanisms in the RAW264.7 murine macrophage cell line. The number of tartrate­resistant acid phosphatase (TRAP)­positive multinucleated cells were counted and the bone resorption area was estimated. In addition the expression levels of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) mRNA and osteoclast­specific genes, including TRAP, matrix metalloproteinase 9, cathepsin K and osteoclast­associated receptor, were examined using reverse transcription­quantitative polymerase chain reaction. The nuclear factor­κB (NF­κB) and mitogen­activated protein kinase (MAPK) signaling pathways were also investigated using western blotting. The results showed that amiloride significantly reduced the number of TRAP­positive multinucleated cells as well as the bone resorption area. Amiloride also downregulated the expression of NFATc1 mRNA and inhibited the expression of osteoclast­specific genes. A possible underlying mechanism may be that amiloride suppresses the degradation of the inhibitor of NF­κB and blocks the activation of c­Jun N­terminal kinase, extracellular signal­regulated kinase and p38, thus implicating the NF­κB and MAPK pathway is this process. In conclusion, the current data suggest that amiloride is a strong inhibitor of osteoclast differentiation, indicating a novel indication for amiloride in the treatment of bone­loss­related diseases.

Increasing trends in central obesity among Chinese adults with normal body mass index, 1993-2009.

BACKGROUND: Central obesity is thought to be more pathogenic than overall obesity and studies have shown that the association between waist circumference (WC) and mortality was strongest in those with a normal body mass index (BMI). The objective of our study was to determine secular trends in the prevalence of central obesity (WC ≥ 90 cm for men and ≥ 80 cm for women) among Chinese adults with normal BMI from 1993 to 2009 and to examine the impact of performance of combined BMI and WC on the prevalence of obesity in Chinese adults. METHODS: We used data from the China Health and Nutrition Survey (CHNS) conducted from 1993 to 2009. From which we included a total of 52023 participants aged ≥ 18 years. RESULTS: The age-standardized prevalence of central obesity among Chinese adults with BMI < 25 kg/m² increased from 11.9% in 1993 to 21.1% in 2009 (P for linear trend <0.001). The upward trends were noted in both genders, all ages, rural/urban settings, and education groups (all P for linear trend <0.001), with greater increments in men, participants aged 18-64 years, and rural residents (P for interaction terms survey × sex, survey × age, and survey × rural/urban settings were 0.042, 0.003, and < 0.001, respectively). Trends in the prevalence of central obesity were similar when a more stringent BMI < 23 kg/m² cut point (Asian cut point) was applied. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. More than 65% individuals with obesity would be missed if solely BMI was measured. CONCLUSIONS: We observed an upward trend in the prevalence of central obesity among participants with normal BMI irrespective of sex, age, rural/urban settings, and education level. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. Approximately two thirds of the individuals with obesity would be missed if WC was not measured. It is, therefore, urgent to emphasize the importance of WC as a measure to monitor the prevalence of obesity.