دورية
Evidence That c-src Is Involved in the Process of Osteoclastic Bone Resorption
| العنوان: | Evidence That c-src Is Involved in the Process of Osteoclastic Bone Resorption |
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| المؤلفون: | Hall, T.J., Schaeublin, M., Missbach, M. |
| المصدر: | Biochemical and Biophysical Research Communications; March 31, 1994, Vol. 199 Issue: 3 p1237-1244, 8p |
| مستخلص: | Transgenic mice lacking a functional c-src gene have osteopetrosis, a bone disorder characterized by defective osteoclast function. We have investigated the effects of selective protein tyrosine kinase inhibitors that are known to inhibit c-src, on osteoclast activity in the bone slice assay. Geldanamycin, herbimycin A and monorden (0.001 - 10 µM) all dose-dependently inhibited bone resorption with IC50 values of 8, 70 and 86 nM, respectively. At concentrations of 0.001 - 1 µM, the compounds were not cytotoxic as judged by osteoclast morphology and survival on bone slices. In order to determine whether c-src plays a role in signal transduction associated with osteoclast activation prior to bone resorption commencing, or in the resorptive process itself, we performed kinetic experiments using human calcitonin as a positive control. Calcitonin inhibited all bone resorption subsequent to its addition at t = 0, 3 or 6 hr (100%, ~90% and ~50% inhibition, respectively), after the start of the 24 hr bone slice assay. Similar results were obtained with herbimycin A and geldanamycin (1 µM) added at t = 0, 3 or 6 hr, and with monorden (1 µM) added at t = 0 and 6 hr. These results indicate that c-src plays a crucial and continuous role in the process of osteoclastic bone resorption, most likely related to the translocation and/or fusion of exocytic vesicles to the ruffled border membrane.Copyright 1994, 1999 Academic Press |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 0006291X 10902104 |
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| DOI: | 10.1006/bbrc.1994.1363 |