Association of metalloproteinases, tissue inhibitors of matrix metalloproteinases, and proteoglycans with development, aging, and osteoarthritis processes in mouse temporomandibular joint

Abstract

The temporomandibular joint (TMJ) is an important growth and articulation center in the craniofacial complex. In aging it develops spontaneous degenerative osteoarthritic (OA) lesions. Metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPS) play key roles in extracellular matrix remodeling and degradation. Gelatinase activities and immunohistochemical localization of MMP-2, -3, -8, -9, and -13 and TIMP-1 and -2 were examined in mandibular condyle cartilage of neonatal mice up to 18 months old. The most intense immunostaining for all enzymes and TIMPs and the peak of gelatinase activities were found in animals in the stages of early growth (1 week to 3 months) followed by a decrease during maturation and aging. However, clusters of positively immunoreactive chondrocytes were detected in cartilages of old animals displaying OA lesions. Positive safranin-O staining, indicative of sulfated proteoglycans (PGs), was prominent in the TMJ of newborn mice up to 3 months old followed by reduction during maturation and aging, except in regions displaying OA lesions. Temporal codistribution of PGs, MMPs, and TIMPs during skeletal maturation reflected an active growth phase, whereas their reduction coincided with the more quiescent articulating and maintenance phase in the joint cartilage. Osteoarthritic lesions were associated with both increased PG synthesis and MMP immunoreactivity, indicating limited repair activity during initial stages of osteoarthritis.

Comparison of age-dependent expression of aggrecan and ADAMTSs in mandibular condylar cartilage, tibial growth plate, and articular cartilage in rats

“…Cell volume increases as chondrocytes diVerentiate during this process (Luder et al 1988). Besides the expression of ADAMTSs, chondrocytes produce several types of MMP during growth (Bae et al 2003;Gepstein et al 2003). Therefore, once deposited, ECM components such as type II collagen and aggrecan are degraded by aggrecanases in combination with MMPs.…”

Exposure to pro-inflammatory cytokines upregulates MMP-9 synthesis by mesenchymal stem cells-derived osteoprogenitors

“…Bone loss in RA occurs both in the subchondral bone in the joints and throughout the skeleton as a result of the release of proteinases, mainly MMPs, and pro-inXammatory cytokines (IL-1, TNF-), which are responsible for cartilage and bone destruction (Gepstein et al 2002(Gepstein et al , 2003. As a result, inXammation activity becomes an independent risk factor for osteoporosis in RA (Gepstein et al 2002(Gepstein et al , 2003Ginaldi et al 2005). The current knowledge targets elevated osteoclasts activity due to increased inXammatory process as one of the major reasons for increased bone resorption seen in diseases like RA and osteoporosis.…”

The Changes in Matrix Metalloproteinases and Collagens Expression of Rat Articular Cartilage after Continuous Mandibular Advancement: Immunohistochemical Study

“…The intracellular expression of MMP-13, which is a key molecule in the regulation of endochondral ossification, hah a significant positive increase in the layer of proliferative, differentiation and hypertrophy in the experimental group in active and retention period [43,44]. This revealed the localization of MMP-13 in the layer of condylar cartilage and the specific time of its appearance during the developmental stage which might be essential by chondrocytes enlargement and rapid proliferation and differentiation in condylar cartilage that occurs at a stage before the onset of mineralization [10,11].…”