Artesunate inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents LPS-induced bone loss in vivo.

Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL-induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF-κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)-induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL-induced osteoclastogenesis by suppressing the NF-κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases.

Monocrotaline Suppresses RANKL-Induced Osteoclastogenesis In Vitro and Prevents LPS-Induced Bone Loss In Vivo.

BACKGROUND/AIMS: Extensive osteoclast formation plays a critical role in bone diseases, including rheumatoid arthritis, periodontitis and the aseptic loosening of orthopedic implants. Thus, identification of agents that can suppress osteoclast formation and bone resorption is important for the treatment of these diseases. Monocrotaline (Mon), the major bioactive component of crotalaria sessiliflora has been investigated for its anti-cancer activities. However, the effect of Mon on osteoclast formation and osteolysis is not known. METHODS: The bone marrow macrophages (BMMs) were cultured with M-CSF and RANKL followed by Mon treatment. Then the effects of Mon on osteoclast differentiation were evaluated by counting TRAP (+) multinucleated cells. Moreover, effects of Mon on hydroxyapatite resorption activity of mature osteoclast were studied through resorption areas measurement. The involved potential signaling pathways were analyzed by performed Western blotting and quantitative real-time PCR examination. Further, we established a mouse calvarial osteolysis model to measure the osteolysis suppressing effect of Mon in vivo. RESULTS: In this study, we show that Mon can inhibit RANKL-induced osteoclast formation and function in a dose-dependent manner. Mon inhibits the expression of osteoclast marker genes such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Furthermore, Mon inhibits RANKL-induced the activation of p38 and JNK. Consistent with in vitro results, Mon exhibits protective effects in an in vivo mouse model of LPS-induced calvarial osteolysis. CONCLUSION: Taken together our data demonstrate that Mon may be a potential prophylactic anti-osteoclastic agent for the treatment of osteolytic diseases caused by excessive osteoclast formation and function.

Morphological, physiological, and structural responses of two species of artemisia to NaCl stress.

Effects of salt stress on Artemisia scoparia and A. vulgaris "Variegate" were examined. A. scoparia leaves became withered under NaCl treatment, whereas A. vulgaris "Variegate" leaves were not remarkably affected. Chlorophyll content decreased in both species, with a higher reduction in A. scoparia. Contents of proline, MDA, soluble carbohydrate, and Na(+) increased in both species under salt stress, but A. vulgaris "Variegate" had higher level of proline and soluble carbohydrate and lower level of MDA and Na(+). The ratios of K(+)/Na(+), Ca(2+)/Na(+), and Mg(2+)/Na(+) in A. vulgaris "Variegate" under NaCl stress were higher. Moreover, A. vulgaris "Variegate" had higher transport selectivity of K(+)/Na(+) from root to stem, stem to middle mature leaves, and upper newly developed leaves than A. scoparia under NaCl stress. A. vulgaris "Variegate" chloroplast maintained its morphological integrity under NaCl stress, whereas A. scoparia chloroplast lost integrity. The results indicated that A. scoparia is more sensitive to salt stress than A. vulgaris "Variegate." Salt tolerance is mainly related to the ability of regulating osmotic pressure through the accumulation of soluble carbohydrates and proline, and the gradient distribution of K(+) between roots and leaves was also contributed to osmotic pressure adjustment and improvement of plant salt tolerance.

[Three-dimensional kinematic characteristics of motion of lower limb joints in stroke patients with chronic hemiplegia].

OBJECTIVE: To quantitatively analyze the three-dimensional kinematic features of the motion of lower limb joints in stroke patients with chronic hemiplegia. METHODS: A three-dimensional motion analysis system was used to measure the gait of 39 patients with chronic hemiplegia due to stroke, 12 males and 15 females, aged 57.11 +/- 9.58 (43 - 75), who could walk at least 10 m independently without a walking aid, and 27 sex and age-matched non-disabled controls. RESULTS: The values of range of motion (ROM) of hip and knee of the stroke patients were 34 - 39 degrees and 50 - 58 degrees respectively, both significantly lower than those of the controls (40 - 45 degrees and 65 - 72 degrees respectively, both P < 0.01), however, the ROM of ankle of the stroke patients was 22 - 28 degrees, not significantly different from that of the controls (26 - 30 degrees, P > 0.05). The hip extension and ankle dorsiflexion of the stroke patients were 1 - 4 degrees and 8 - 10 degrees respectively, both significantly lower than those of the controls (14 - 19 degrees and 14 - 16 degrees respectively, both P < 0.01), however, the genuflex of the stroke patients was 59 - 66 degrees, not significantly different from that of the controls (65 - 69 degrees, P > 0.05). The ratio of the weak and sound sides (W/S) of hip extension and the W/S value of ankle dorxiflexion of the stroke patients were 0.33 +/- 0.40 and 0.65 +/- 0.22, both significantly lower than those of the controls (1.06 +/- 0.29 and 0.99 +/- 0.27, both P < 0.01), however, the W/S value of genuflex of the stroke patients was 0.90 +/- 0.23, not significantly different from that of the controls (1.01 +/- 0.07, P < 0.05). CONCLUSION: Lack of motion of lower limb joints in the weak side and asymmetry of lower limb motion between the weak and sound sides are the characteristics of the hemiplegic gait in stroke.