No abstract available.
Animals ; Bone Density ; Cathepsin K ; Cathepsins ; Models, Animal ; Osteoporosis

No abstract available.
Animals ; Bone Density ; Cathepsin K ; Cathepsins ; Models, Animal ; Osteoporosis

No abstract available.
Animals ; Bone Density ; Cathepsin K ; Cathepsins ; Models, Animal ; Osteoporosis

No abstract available.
Animals ; Bone Density ; Cathepsin K ; Cathepsins ; Models, Animal ; Osteoporosis

No abstract available.
Animals ; Bone Density ; Cathepsin K ; Cathepsins ; Models, Animal ; Osteoporosis

OBJECTIVEThis study aims to explore the effect of Notch signaling depression on the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis of RAW264.7 cells.

METHODSMice RAW264.7 cells were cultured and differentiated into osteoclasts with the induction of RANKL. The expressions of Notch1, Notch2, Deltal, Jagged1, Hes1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K genes during osteoclastogenesis were analyzed using real-time polymerase chain reaction. Osteoclast formation was analyzed using TRAP assay with suppression of Notch receptors by a selective γ-secretase inhibitor (GSI).

RESULTSNotch1, Notch2, Delta1, Jagged1, and Hes1 expressions in RAW264.7 cells were upregulated following 50 ng · mL-RANKL stimulation for 3 d, concomitant with the expression of the osteoclast differentiation markers TRAP and Cathepsin K. Notch2 and Jagged1 had the most remarkable increase in the Notch family members. GSI inhibited RANKL-induced osteoclastogenesis of RAW264.7 cells and Hes1 expression dose-dependently.

CONCLUSIONNotch signaling activation may promote RANKL-induced osteoclastogenesis of RAW264.7 cells.

Animals ; Cathepsin K ; Cell Differentiation ; In Vitro Techniques ; Mice ; Osteoclasts ; Osteogenesis ; RANK Ligand

Osteoporosis, the sixth most common disease in the world, is bringing increasingly serious harm to people's health. Cathepsin K, which plays an important role in bone resorption, is a potential target in the treatment of osteoporosis. Total flavonoids, the active ingredients in Rhizoma Drynariae, have shown obvious, therapeutic effect on osteoporosis. In previous studies, it was presumed that the mechanism for the therapeutic effect was through inhibiting the expression of Cathepsin K. However, there are still no detailed reports on some key issues such as the specific inhibitory results of total flavonoids on Cathepsin K and the pathway of inhibition and so on. Based on previous studies on total flavonoids from Rhizoma Drynariae, the pathway for the effect of, total flavonoids inhibiting Cathepsin K and their interventional value on Cathepsin K were analyzed in this paper, so as to explore the interventional feasibility and value of total flavonoids in Rhizoma Drynariae on Cathepsin K.
Cathepsin K ; metabolism ; Flavonoids ; therapeutic use ; Humans ; Molecular Targeted Therapy ; Osteoporosis ; drug therapy ; enzymology ; Polypodiaceae ; chemistry ; Rhizome ; chemistry

OBJECTIVETo compare the effects of 8-prenylnaringenin (PNG) and naringenin (NG) on the activity and apoptosis of osteoclasts cultured in vitro, in order to study physiological activity of 8-prenyl perssad.

METHODOsteoclasts were separated from long-limb bones of newly born rabbits, cultured in alpha-MEM containing 10% FBS, and then added with PNG and NG with the concentration of 1 x 10(-5) mol x L(-1). They were stained with TRAP and determined for enzymatic activity with TRAP after 4 d, and analyzed by toluidine blue staining after 7 d. The apoptotic osteoclasts were analyzed by Annexin V-FITC staining after 2, 4, 8, 12, 24, 36, and 48 hours, to observe their apoptosis. Their total RNAs were extracted, and analyzed for TRAP and Cathepsin K expressions by Real-time RT-PCR.

RESULTCompared with the control group, both of the PNG group and the NG group showed much less osteoclasts (TRAP positive cells), lower TRAP activity and TRAP and Cathepin K (CTSK) expression, and smaller number of bone resorption pits and areas. The PNG group show lower indexes than the NG group. Additionally, the PNG group reached the apoptotic peak of osteoclasts at 12 h after drug administration, whereas the NG group reached after 24 h. And the former had more apoptotic cells than the latter.

CONCLUSION8-PNG is much more active than NG in inhibiting the resorption of osteoclasts and inducing apoptosis of osteoclasts. Their only difference lies in 8-prenyl perssad, which is proved to be able to enhance the anti-bone resorption activity of 8-prenylnarigenin.

Acid Phosphatase ; metabolism ; Animals ; Bone Resorption ; prevention & control ; Cathepsin K ; metabolism ; Cells, Cultured ; Flavanones ; pharmacology ; Osteoclasts ; drug effects ; Rabbits

To determine the effect of the tumor necrosis factor-α (TNF-α) in odontoclast formation, we administrated a TNF-α inhibitor in rats with diabetes rats with periodontitis. The rats included in the study were divided into three groups: control rats without diabetes or periodontitis (the C group), rats with periodontitis and diabetes (the PD group), and rats with periodontitis and diabetes treated by infliximab, the TNF inhibitor (the PD+infliximab group). The PD and PD+ infliximab groups received intravenous administrations of streptozotocin (STZ, 50 mg/kg) to induce diabetes. After 7 days of STZ injections, the mandibular first molars were ligatured to induce periodontitis. The PD+infliximab group was intrapenitoneally administrated by infliximab (5 mg/kg). On days 3 and 20 after the ligature administration, odontoclast formation along root surfaces was evaluated by tartrate resistant acid phosphatase (TRAP) staining and cathepsin K immunohistochemistry. On day 3, the number of TRAP- and cathepsin K-positive cells increased more so in the PD group than in the C group. The PD+infliximab group showed a lower number of positive cells than the PD group. There was no difference in all the groups on day 20. On day 3, the cathepsin-K positive multinucleated and mononucleated cells were higher in the PD group than in the C group. The number of cathepsin-K positive multinucleated cells was lower in the PD+infliximab group than in the PD group. The PD group showed more cathepsin K-positive cells in the furcation and distal surfaces than the c group. The Cathepsin K-positive cells of the PD+infliximab group were lower than that of the PD group in furcation. These results suggest that TNF-α stimulates odontoclast formation in diabetes with periodontitis.
Acid Phosphatase ; Administration, Intravenous ; Animals ; Cathepsin K ; Cathepsins ; Immunohistochemistry ; Infliximab ; Ligation ; Molar ; Necrosis ; Osteoclasts* ; Periodontitis* ; Rats* ; Streptozocin

Osteoporosis is a common senile disease that results in fragility fractures. With an ageing population, the medical and socioeconomic effect of osteoporosis, particularly postmenopausal osteoporosis, will increase further. Currently, good anti-fracture data supports many available anti-resorptive and anabolic drugs including bisphosphonates, selective estrogen receptor modulators, and recombinant human parathyroid hormones. Calcium and vitamin D are also essential treatments for the prevention and treatment of osteoporosis. Although, bisphosphonate is the cornerstone of osteoporosis treatment and is considered as the first line of therapy, their duration of therapy and long-term safety is under question. Novel agents, particularly denosumab, inhibitors of cathepsin K, andanabolic agents that act on Wnt signaling, will increase the therapeutic options for clinicians in the coming years.
Antibodies, Monoclonal, Humanized ; Calcium ; Cathepsin K ; Diphosphonates ; Female ; Humans ; Osteoporosis ; Osteoporosis, Postmenopausal ; Selective Estrogen Receptor Modulators ; Vitamin D ; Denosumab