1.Response: The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis.
Seung Hun LEE ; Jung Min KOH ; Young Sun LEE ; Beom Jun KIM ; Je Yong CHOI ; Ghi Su KIM
Endocrinology and Metabolism 2012;27(1):107-107
No abstract available.
Animals
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Bone Density
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Cathepsin K
;
Cathepsins
;
Models, Animal
;
Osteoporosis
2.Response: The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis.
Seung Hun LEE ; Jung Min KOH ; Young Sun LEE ; Beom Jun KIM ; Je Yong CHOI ; Ghi Su KIM
Endocrinology and Metabolism 2012;27(1):107-107
No abstract available.
Animals
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Bone Density
;
Cathepsin K
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Cathepsins
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Models, Animal
;
Osteoporosis
3.Letter: The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis.
Endocrinology and Metabolism 2012;27(1):105-106
No abstract available.
Animals
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Bone Density
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Cathepsin K
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Cathepsins
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Models, Animal
;
Osteoporosis
4.Letter: The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis.
Endocrinology and Metabolism 2012;27(1):105-106
No abstract available.
Animals
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Bone Density
;
Cathepsin K
;
Cathepsins
;
Models, Animal
;
Osteoporosis
5.The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change of Bone Mineral Density in Animal Model of Osteoporosis.
Endocrinology and Metabolism 2011;26(4):295-296
No abstract available.
Animals
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Bone Density
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Cathepsin K
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Cathepsins
;
Models, Animal
;
Osteoporosis
6.Notch signaling promotes receptor activator of nuclear factor kappa B ligand-induced ostoclastogenesis of RAW264.7 cells in vitro.
West China Journal of Stomatology 2015;33(1):25-28
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
7.Current and Upcoming Treatments for Osteoporosis.
Journal of Rheumatic Diseases 2012;19(1):4-10
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
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Calcium
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Cathepsin K
;
Diphosphonates
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Female
;
Humans
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Osteoporosis
;
Osteoporosis, Postmenopausal
;
Selective Estrogen Receptor Modulators
;
Vitamin D
;
Denosumab
8.TNF-α Inhibitor Reduces Odontoclast Formation in Diabetes Rats with Ligature-Induced Periodontitis.
Ji Hye KIM ; Ae Ri KIM ; Yun Hui CHOI ; Dong Eun LEE ; Gye Hyeong WOO ; Eun Jung BAK ; Yun Jung YOO
International Journal of Oral Biology 2017;42(3):137-142
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
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Animals
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Cathepsin K
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Cathepsins
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Immunohistochemistry
;
Infliximab
;
Ligation
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Molar
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Necrosis
;
Osteoclasts*
;
Periodontitis*
;
Rats*
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Streptozocin
9.The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis.
Seung Hun LEE ; Jung Min KOH ; Young Sun LEE ; Beom Jun KIM ; Je Yong CHOI ; Ghi Su KIM
Endocrinology and Metabolism 2011;26(4):303-309
BACKGROUND: We hypothesized that combination therapy of cathepsin K inhibitor (CTKi) and human parathyroid hormone (1-34) (teriparatide, PTH) would overcome the coupling phenomenon of bone resorption and formation and thus may rapidly increase bone mass. METHODS: We selected a dose of zoledronic acid (ZA) that had shown similar effects with CTKi on body bone mineral density (BMD) change during the preliminary experiment. Female mice were subjected to ovariectomized (OVX control) or a sham operation (SHAM group). The mice were treated with CTKi (CTKi group), ZA (ZA group), PTH (PTH group) or with a combination of PTH with ZA (ZA + PTH group) or CTKi (CTKi + PTH group) for 8 weeks. Total BMD was measured before the operation and at 4 and 8 weeks. RESULTS: In the preliminary results, 10 microg/kg of ZA showed similar BMD changes with CTKi. Compared with the OVX control, BMD in the SHAM, ZA, CTKi, PTH, ZA + PTH, and CTKi + PTH groups was significantly increased after treatment. BMD in the CTKi + PTH group, but not in the ZA + PTH group increased more significantly than in the PTH group at the end of treatment. Compared with the OVX control, changes in BMD in the SHAM, ZA, CTKi, PTH, ZA + PTH, and CTKi + PTH groups increased significantly after 8 weeks of treatment. The change in BMD in the CTKi + PTH group, but not in the ZA + PTH group was more significantly increased than the change in BMD in the PTH group. CONCLUSION: When combined with PTH, CTKi augmented the anabolic action of PTH. Therefore, combination therapy with CTKi and PTH might be a new therapeutic modality capable of overcoming the coupling phenomenon, thereby markedly and rapidly increasing bone mass.
Animals
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Bone Density
;
Bone Resorption
;
Cathepsin K
;
Cathepsins
;
Diphosphonates
;
Female
;
Humans
;
Imidazoles
;
Mice
;
Models, Animal
;
Osteoporosis
;
Parathyroid Hormone
;
Salicylamides
;
Teriparatide
10.New Antiresorptive Therapies for Postmenopausal Osteoporosis.
Journal of Menopausal Medicine 2015;21(1):1-11
Osteoporosis is a systemic skeletal disease whose risk increases with age and it is common among postmenopausal women. Currently, almost all pharmacological agents for osteoporosis target the bone resorption component of bone remodeling activity. Current antiresorptive agents are effective, but the effectiveness of some agents is limited by real or perceived intolerance, longterm adverse events (AEs), coexisting comorbidities, and inadequate long-term adherence. New antiresorptive therapies that may expand options for the prevention and treatment of osteoporosis include denosumab, combination of conjugated estrogen/bazedoxifene and cathepsin K inhibitors. However, the long-term efficacy and AEs of these antiresorptive therapies need to be confirmed in studies with a longer follow-up period.
Bone Density Conservation Agents
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Bone Remodeling
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Bone Resorption
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Cathepsin K
;
Comorbidity
;
Female
;
Humans
;
Osteoporosis
;
Osteoporosis, Postmenopausal*
;
Postmenopause
;
Denosumab