The osteoclast resorbs bone by lowering the pH in the resorption lacuna, which is followed by secretion of proteolytic enzymes. One of the enzymes taken to be essential in resorption is the cysteine proteinase, cathepsin K. Some immunolabeling and enzyme inhibitor data, however, suggest that other cysteine proteinases and/or proteolytic enzymes belonging to the group of matrix metalloproteinases (MMPs) may participate in the degradation. In this study, we investigated whether, in addition to cathepsin K, other enzymes participate in osteoclastic bone degradation.
In bones obtained from mice deficient for cathepsin K, B, or L or a combination of K and L, the bone-resorbing activity of osteoclasts was analyzed at the electron microscopic level. In addition, bone explants were cultured in the presence of different selective cysteine proteinase inhibitors and an MMP inhibitor, and the effect on resorption was assessed. Because previous studies showed differences in resorption by calvarial osteoclasts compared with those present in long bones, in all experiments, the two types of bone were compared. Finally, bone extracts were analyzed for the level of activity of cysteine proteinases and the effect of inhibitors hereupon.
The analyses of the cathepsin-deficient bone explants showed that, in addition to cathepsin K, calvarial osteoclasts use other cysteine proteinases to degrade bone matrix. It was also shown that, in the absence of cathepsin K, long bone osteoclasts use MMPs for resorption. Cathepsin L proved to be involved in the MMP-mediated resorption of bone by calvarial osteoclasts; in the absence of this cathepsin, calvarial osteoclasts do not use MMPs for resorption. Selective inhibitors of cathepsin K and other cysteine proteinases showed a stronger effect on calvarial resorption than on long bone resorption.
Our gums' own cells produce the substances that lead to the degeneration of the jawbone. This is one of the findings in a dissertation that Py Palmqvist will defend at Umea University in Sweden on January 19. The findings are important to our understanding of how inflammation leads to loosening of the teeth, arthritic rheumatism, and prostheses detaching from the body.
The dissertation shows that certain signal substances in the body, so-called cytokines, have the ability to stimulate the cells in bones to degenerate and that these cytokines are produced not only by white blood corpuscles but also by cells in the gums, so-called gum fibroblasts. The production of the cytokine interleukin-6 and its closest relatives, interleukin-11 and leukemia inhibitory factor, is stimulated by certain inflammatory cytokines and is inhibited by other anti-inflammatory cytokines from white blood corpuscles. The findings are important to our understanding of the interplay between local cells in the gums and white blood corpuscles immigrating from the blood that regulates the degradation of bone in diseases involving loosening of the teeth.
The skeleton of a healthy adult human is constantly being renewed, with some parts degrading and being replaced by new bone, on the one hand, to exchange old bone for new bone and, on the other hand, to adapt the structure of the bone to new loads. This occurs at a rate of about 10 percent of the entire bone tissue being replaced each year. In pathological conditions, the reconstruction process can be altered so that the degradation increases and the new growth cannot replace all the degenerated bone. This occurs, for example, in most of the bones in the bodies of patients afflicted with osteoporosis as a result of changes in the amounts of sex hormones. It also occurs locally in certain parts of the skeleton where inflammatory processes are underway. In patients with inflamed gums, the inflammation process can affect the replacement of the bone around the teeth in the jaws so that the bone is lost. The teeth will then become looser and looser until they fall outgum inflammation has led to loosening of the teeth.