Cathepsin K, Osteoclastic Resorption, and Osteoporosis Therapy

2001 ◽  
Vol 16 (10) ◽  
pp. 1747-1749 ◽  
Author(s):  
Mone Zaidi ◽  
Bruce Troen ◽  
Baljit S. Moonga ◽  
Etsuko Abe
2010 ◽  
Vol 26 (4) ◽  
pp. 435-449 ◽  
Author(s):  
Keiichi Kanayama ◽  
Wantida Sriarj ◽  
Hitoyata Shimokawa ◽  
Keiichi Ohya ◽  
Yutaka Doi ◽  
...  

Previous studies have demonstrated that carbonate apatite (CA) is superior to hydroxyapatite (HA) and β-tricalciumphosphate (β-TCP) with regard to osteoclastic resorption, but evidence on osteoclast and osteoblast response remains controversial. In the present study, the expression of bone related mRNA is examined on CA, HA, β-TCP, and titanium plates. ICR mouse osteoblast cells are cocultured with ICR mouse bone marrow cells. Crude osteoclast-like cell-rich suspensions are then seeded onto plates and cultured for 48 h. Total RNA is extracted and mRNA expression is examined by real-time RT-PCR. Amounts of vacuolar-type ATPase, cathepsin K, and TRAP mRNA are significantly greater on CA than on the other plates. The amount of osteoprotegerin mRNA is significantly greater on CA than on the other plates. RANKL mRNA expression, which is generally regarded as an osteoblast maker, varies with material, but shows no significant differences between CA and the other plates. The formation and activity of osteoclasts is greater with CA than with the other plates. Thus, CA is superior to β-TCP as a bioresorbable bone substitute for tissue engineering.


2001 ◽  
Vol 276 (15) ◽  
pp. 11507-11511 ◽  
Author(s):  
Ian E. James ◽  
Robert W. Marquis ◽  
Simon M. Blake ◽  
Shing Mei Hwang ◽  
Catherine J. Gress ◽  
...  

Cathepsins K and L are related cysteine proteases that have been proposed to play important roles in osteoclast-mediated bone resorption. To further examine the putative role of cathepsin L in bone resorption, we have evaluated selective and potent inhibitors of human cathepsin L and cathepsin K in anin vitroassay of human osteoclastic resorption and anin situassay of osteoclast cathepsin activity. The potent selective cathepsin L inhibitors (Ki= 0.0099, 0.034, and 0.27 nm) were inactive in both thein situcytochemical assay (IC50> 1 μm) and the osteoclast-mediated bone resorption assay (IC50> 300 nm). Conversely, the cathepsin K selective inhibitor was potently active in both the cytochemical (IC50= 63 nm) and resorption (IC50= 71 nm) assays. A recently reported dipeptide aldehyde with activity against cathepsins L (Ki= 0.052 nm) and K (Ki= 1.57 nm) was also active in both assays (IC50= 110 and 115 nm, respectively) These data confirm that cathepsin K and not cathepsin L is the major protease responsible for human osteoclastic bone resorption.


2007 ◽  
Vol 37 (11) ◽  
pp. 18
Author(s):  
SHERRY BOSCHERT
Keyword(s):  

2015 ◽  
Vol 24 (04) ◽  
pp. 215-218
Author(s):  
B. Obermayer-Pietsch ◽  
V. Schwetz

ZusammenfassungKnochenumbauparameter können zusätzliche Informationen zur Abschätzung der Dynamik des Knochenstoffwechsels in der Osteoporosediagnostik nebst Knochendichte, den klinischen Daten und Routine-Laborparametern liefern. Zu den Aufbaumarkern des Knochenstoffwechsels zählen Prokollagen Typ 1 N-terminales Propeptid (P1NP), die knochenspezifische alkalische Phosphatase (bALP) und Osteokalzin (OC), zu den Abbaumarkern des Knochenstoffwechsels gehören Pyridinolin (PYD) und Desoxypyridinolin (DPD), N-terminales Kollagen-Typ-I-Telopeptid (NTX) und C-terminales Kollagen-Typ-ITelopeptid (CTX), β-CrossLaps (β-CTX), die Tartrat-resistent saure Phosphatase (TRAP5b) sowie Cathepsin K. Das Einsatzgebiet liegt vor allem in der Verlaufsbeurteilung nach Einleitung einer Osteoporosetherapie und im Compliance-Monitoring. Knochenumbaumarker stellen jedoch derzeit keine alleinige Entscheidungsgrundlage zur Initiierung einer Therapie dar. In der Hämatoonkologie scheinen hohe Knochenabbaumarker mit einem höheren Rezidivrisiko bzw. einem höheren Risiko für skelettassoziierte Ereignisse verbunden zu sein.


2020 ◽  
Author(s):  
Keyword(s):  

2020 ◽  
pp. 39-43
Author(s):  
A. V. Voronkina ◽  
T. A. Raskina ◽  
M. V. Letaeva ◽  
Yu. V. Averkieva ◽  
O. S. Malyshenko ◽  
...  

The development of atherosclerosis is closely related to the calcification of the vessel intima and fibrous plaques, being a complex and multifactorial process, in which the markers of bone formation and resorption play an important role. Objective. To study the biochemical markers of bone metabolism in men with stable coronary heart disease (CHD). Material and methods. The study included 102 men with verified CHD. Data were evaluated by densitometry, coronary angiography, multispiral computed tomography, color duplex scanning of brachiocephalic arteries, serum lipids (total cholesterol, triglycerides [TG], high-density [LHD] and low-density lipoprotein cholesterol), concentrationsin the blood of osteocalcin (OC), bone alkaline phosphatase (BAP), cathepsin K and C-telopeptides (CTx). Results. Concentrations of BAP, cathepsin K and CTx in patients with CHD were significantly higher than in men without CHD. The concentration of OC in men with normal bone mineral density was significantly lower than in patients with osteopenic syndrome. There was a direct correlation between OC and antiatherogenic HDL cholesterol and the inverse correlation between OC and TG, CTx and TG. There was no correlation between the level of bone remodeling markers and coronary artery (CA) lesion variant and the severity of coronary atherosclerosis on SYNTAX scale. The correlation analysis did not reveal the connection of biochemical markers of bone metabolism with the severity of coronary atherosclerosis and calcification and thickness of intima-media complex of carotid arteries. Absolute values of bone formation indices (BAP, OC) were significantly higher in patients with severe СA calcification than in patients without signs of calcification. Summary. Increased rates of osteogenesis and osteoresorption characterize the accelerated process of bone metabolism and indicate in favor of high rates of bone loss in men with CHD, which confirms the likelihood of common pathophysiological mechanisms of bone resorption and arterial calcification.


2014 ◽  
Author(s):  
Nicolas Bonnet ◽  
Lee Duong ◽  
Serge Ferrari
Keyword(s):  

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