In vitro sensitivity of the three mammalian collagenases to tetracycline inhibition: relationship to bone and cartilage degradation.

摘要: Abstract There are at least nine tetracycline (TC) analogs (both antimicrobial and nonantimicrobial) with documented capacity to inhibit, both in vitro vivo, the connective tissue degrading activity of matrix metalloproteinases (MMPs). Of three MMPs that can degrade native helical collagens, MMP-13 (initially identified as rat osteoblast human breast cancer collagenase, now known also be expressed by cartilage bone cells) is most sensitive TC inhibition (IC 50 values generally less than 1 μg/mL); TCs inhibit collagenolytic well gelatinolytic this enzyme. The IC for MMP-8 (neutrophil collagenase) ranges from 15 86 μg/mL depending on assay conditions choice TC, whereas fibroblast enzyme (MMP-1) requires levels excess 200 (except CMT-3). compounds highly effective against inhibitory glycosaminoglycan release interleukin-1-stimulated explants culture. current data correlate with: (i) literature resorption isolated osteoclasts; (ii) avian tibial organ culture; (iii) dramatic ability destruction many models (rats have only MMP-13, no MMP-1). By carefully selecting a TC-based MMP inhibitor controlling dosages, it should possible pathologically excessive and/or activity, especially causing erosion, without affecting constitutive MMP-1 needed remodeling normal host function; regard, newly developed CMTs (especially CMT-8 and, lesser extent, CMT-3 -7) appear effective.