Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteoclasts require matrix metalloproteinase (MMP) activity and cathepsin K to resorb bone, but the critical MMP has not been identified. Osteoclasts express MMP-9 and MMP-14, which do not appear limiting for resorption, and the expression of additional MMPs is not clear. MMP-12, also called metalloelastase, is reported only in a few cells, including tissue macrophages and hypertrophic chondrocytes. MMP-12 is critical for invasion and destruction in pathologies such as aneurysm and emphysema. In the present study, we demonstrate that osteoclasts express MMP-12, although only in some situations. Northern blots show that highly purified rabbit osteoclasts in culture express MMP-12 at the same level as macrophages, whereas in situ hybridizations performed on rabbit bone do not show any MMP-12 expression in osteoclasts whatever the bone type. In contrast, in situ hybridizations performed on mouse bone show MMP-12 expression in osteoclasts in calvariae and long bones. We also demonstrate that recombinant MMP-12 cleaves the putative functional domains of osteopontin and bone sialoprotein, two bone matrix proteins that strongly influence osteoclast activities, such as attachment, spreading and resorption. Furthermore, we investigated the role of MMP-12 in bone resorption and osteoclast recruitment by comparing MMP-12 knockout and wild-type mice in specialized culture models known to depend on MMP activity, as well as in the ovariectomy model, and we did not find any indication for a limiting role of MMP-12 in these processes. In conclusion, we found that osteoclasts are able to express MMP-12, but MMP-12 did not appear critical for osteoclast recruitment or resorption. The fact that none of the MMPs identified so far in osteoclasts appears limiting for resorption, gives strength to the hypothesis that the critical MMP for bone solubilization is produced by non-osteoclastic cells.
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PMID:Matrix metalloproteinase-12 (MMP-12) in osteoclasts: new lesson on the involvement of MMPs in bone resorption. 1475 61

Tight skin (Tsk) is an autosomal dominant mutation located on mouse chromosome 2 and is associated with an intragenic duplication of the fibrillin 1 (Fbn1) gene. Mutant mice (Tsk/+) display a tightness of skin in the interscapular region, lung emphysema, myocardial hypertrophy, skeletal overgrowth, and kyphosis. It is hypothesized in this study that in Tsk mice the mutation in Fbn1 alters bone cell metabolism. A detailed study of the Tsk skeletal phenotype revealed that Tsk mice have significantly longer femurs and axial skeleton as well as vertebral abnormalities. Cortical and trabecular bone volumes were significantly decreased in Tsk femurs from 2- and 4-month-old mice (13% and 39%, respectively) as well as trabecular thickness, number, connectivity, and surface area. These skeletal differences were also associated with a reduction in bone mineral density in mutant mice. Expression of the osteoblast-specific genes Col1a1, BSP and OC was examined in marrow stromal cell cultures at various time points. A decrease in the rate of maturation of the Tsk cells was indicated by a delay in the appearance of OC expression. These initial experiments demonstrated a significant role of the fibrillin 1 protein in the extracellular matrix of bone cells.
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PMID:Marfan-like skeletal phenotype in the tight skin (Tsk) mouse. 1770 49