Rhein inhibits ATP-triggered inflammatory responses in rheumatoid rat fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder, which may lead to joint disabilities. So far the pathogenesis of RA remains largely undetermined, and there are still no potent drugs for clinical treatment. Rhein, a natural bioactive anthraquinone derivative, exhibited significant anti-inflammatory activities demonstrated by previous studies. Here we aimed to investigate the effects of rhein on ATP-induced inflammation responses in fibroblast-like synoviocytes isolated from a rat model of collagen induced arthritis (CIA). Our results showed that ATP triggered rapid cytosolic calcium concentration ([Ca2+]c) increase depending on extracellular Ca2+ entry. Given the major P2 subtypes expressed in rat synoviocytes were P2X4 and P2Y2 receptors, ATP-elicited calcium entry should be mainly resulted from activating P2X4. Interestingly, rhein could effectively block the ATP-induced [Ca2+]c increases in a dose-dependent manner. Besides, rhein also suppressed the production of intracellular reactive oxygen species (ROS) induced by ATP in synoviocytes that was resulted from P2X4-mediated Ca2+ entry. Brilliant blue G (BBG), which can block P2X4 receptor at high concentration, showed similar suppressive effects on above responses. Furthermore, in lipopolysaccharide-primed cells, application of ATP synergistically promoted the gene expression of cyclooxygenase-2, interleukin-6 and matrix metalloproteinase-9. Both rhein and BBG attenuated these inflammatory gene expressions enhanced by ATP. Above data together suggested a potential anti-arthritic role of rhein by inhibiting ATP-induced [Ca2+]c increase, ROS production and inflammatory gene expression targeting P2X4 in CIA rat synoviocytes, which will provide a novel insight in the therapy of RA.

Does whole-body vibration with alternative tilting increase bone mineral density and change bone metabolism in senior people?

BACKGROUND AND AIMS: Whole-body vibration (WBV) presents as osteogenic in animal models and young patients, but the effect remains unclear in senior people. The use of alternative tilting during WBV to ameliorate bone mass and bone metabolism, particularly in senior people, has not previously been reported. This study assessed changes in bone mineral density (BMD) and bone metabolism in senior people after six-month treatment of whole-body vibration with alternative tilting (WBVAT). METHODS: Fifty-three senior people (11M/42F, >65 yrs, mean age 77) and 15 adults (4M/11F, 50-60 yrs, mean age 53) were enrolled and assigned randomly to WBVAT (senior: n=27; adult: n=7) and control groups (senior: n=26; adult: n=7), respectively. The WBVAT groups were subjected to vertical vibration (0.5-0.8 g, 45-55 Hz) and alternative tilting (2° tilting angle or 8 mm displacement at 0.4 Hz) 20 minutes per day, 3 days a week, for 6 months. BMD in the lumbar spine and femoral neck was measured at 0, 3 and 6 months, respectively, as well as biochemical markers of bone metabolism, including serum calcium, phosphorus, alkaline phosphatase (ALP), osteocalcin and tartrate resistance acid phosphatase at 0, 1, 3 and 6 months, respectively. RESULTS: After 6-month WBVAT treatment, BMD in the lumbar spine and femoral neck increased significantly by 2.52% and 3.22% for senior people, and 1.63% and 2.05% for adults, respectively. The 6-month WBVAT treatment increased BMD in the senior people, both with and without osteoporosis (OP) and in both men and women, but led to a BMD gain greater in people with OP (p<0.01) and women (p<0.01), respectively. The serum ALP level increased significantly by a net 24.4% in seniors after WBVAT treatment at 3 months; other biochemical markers showed non-significant differences between the WBVAT and control groups. CONCLUSIONS: WBVAT treatment may increase BMD in senior people, particularly those with OP and women. Changes in bone metabolism after WBVAT treatment were not observed in most cases.