Induction of creatine kinase release from cultured osteoclasts via the pharmacological action of aminobisphosphonates
نویسندگان
چکیده
An increase of serum creatine kinase (CK) has been observed in clinical studies of nitrogen-containing aminobisphosphonates (N-BPs). Osteoclasts are thought to be the source of the CK, but there is no clear evidence for the hypothesis. In this study, CK release from rabbit osteoclasts induced by N-BPs was examined in an in vitro culture system. Rabbit bone-derived cells were cultured for 3 days on the N-BPs pretreated cortical bone slices. CK activity in the culture medium was measured at 3 days of culture. The CK activity was increased with all N-BPs at concentrations at which showed antiresorptive activity over 60% inhibition of C-terminal cross-linking telopeptide of type I collagen (CTX-1) release. The maximum induction of CK activity was 2.6 times the control level. The lowest N-BP concentration inducing CK release was 3 times lower than that required to decrease the osteoclast number. Bafilomycin A1, an inhibitor of vacuolar H(+)-ATPase, abrogated all N-BP actions, including CK release. Bone-derived cells except osteoclasts were insensitive to bafilomycin A1, suggesting that osteoclasts were the source of CK. Regarding the time course, CK release occurred after a 1 day lag time and increased steadily until day 3 of culture. These results show that CK release is induced by N-BPs from osteoclasts at concentrations at which N-BPs show antiresorptive activity over 60% inhibition of CTX-1 release in vitro. These findings explain the mechanism of the CK increase induced by clinical use of N-BPs.
منابع مشابه
In Vitro Inhibition of Human Sperm Creatine Kinase by Nicotine, Cotinine and Cadmium, as a Mechanism in Smoker Men Infertility
Background Nicotine, cotinine and cadmium are harmful components of cigarettes that have an effect on human reproductive function. Although the effects of cigarette smoke on male reproductive function is characterized in several articles its mechanism of action is still unknown. In the present study, we investigate the effect of nicotine, cotinine and cadmium on human sperm creatine kinase acti...
متن کاملA New Multistep Induction Protocol for the Transdifferentiation of Bone marrow Stromal Stem Cells into GABAergic Neuron-Like Cells
Background: Bone marrow stromal stem cells (BMSC) are appropriate source of multipotent stem cells that are ideally suited for use in various cell-based therapies. It can be differentiated into neuronal-like cells under appropriate conditions. This study examined the effectiveness of co-stimulation of creatine and retinoic acid in increasing the differentiation of BMSC into GABAergic neuron-lik...
متن کاملIn vitro Effect of Lead, Silver, Tin, Mercury, Indium and Bismuth on Human Sperm Creatine Kinase Activity: a Presumable Mechanism for Men Infertility
Background: The aim of the present study was to investigate the in vitro effects of mercury (Hg+2), lead (Pb+2), silver (Ag+2), tin (Sn+2), bismuth (Bi+3) and indium (In+3) ions on sperm creatine kinase. Methods: creatine kinase was isolated from human sperm homogenates after chromatography on a DEAE cellulose column. Results: At 60 µg ml-1 metal concentration, 70% of the creatine kinase activi...
متن کاملNOVEL REAGENTS FOR CREATINE KINASE
The purpose of this investigation was to develop a simple colorimetric method for creatine kinase (CK). The new method is based on the reaction of creatine, formed enzymatically from creatine phosphate and ADP, with different glyoxal compounds. Hydrated glyoxals, such as para-nitrophenyl, 2-thiophene, 4- biphenyl, 4, 4' -biphenyl,α-naphthyl, β-naphthyl, para-chlorophenyl, and styryl were...
متن کاملcompare the effect of eight weeks of traditional resistance training and TRX on muscle injury indices of inactive Women
Background & Aims: Intense physical activity, despite its various benefits for general health, can cause possible damage to various tissues of the body due to increased oxidative stress through increasing production of reactive species. Muscle bruising and pain is a common experience that occurs after performing unusual and intense activities, especially after resistance and extroverted activit...
متن کامل