On the role of MT1‐MMP, a matrix metalloproteinase essential to collagen remodeling, in murine molar eruption and root growth

Abstract

Although the connective tissues of the periodontium are subject to a high turnover rate, no conclusive evidence has yet emerged that periodontal collagen turnover is essential for the eruption of teeth or for root elongation. These processes were studied in mice deficient in MT1-MMP, a membrane type matrix metalloproteinase essential for remodeling of soft tissue-hard tissue interfaces. Mandibular first molars of deficient mice and their wild-type littermates were subjected to stereological analysis in order to assess root length, eruption and the volume density of phagocytosed collagen in periodontal ligament fibroblasts. The data showed that both eruption and root elongation were severely inhibited in animals lacking the enzyme. We also found, in periodontal ligament fibroblasts from MT1-MMP-deficient mice, a massive age-related accumulation (up to 60-fold over controls) of collagen fibril-containing phagosomes. Phagolysosomes, which represent the next downstream step in collagen fibril degradation by the lysosomal pathway, did not accumulate. These observations indicate that MT1-MMP plays a central role in periodontal remodeling. The stunted root growth and the failure to erupt indicate the important role of the enzyme in tooth development.

MT1‐MMP: A tethered collagenase

“…5D) and mutant mice display progressive fibrosis with extensive resorption of alveolar bone in response to the deficient remodeling of the ligament and ligament bone interface. Formation and longitudinal growth of the roots are severely stunted and as a result the molars fail to erupt and remain submerged in the jaws throughout life (Beertsen et al, 2002). Incisors, on the other hand, continuously develop and erupt unimpeded suggesting, somewhat surprisingly, that the periodontal ligament remodeling required for incisor eruption is independent of MT1-MMP.…”

Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption

“…Some studies have suggested that the abnormal expression of MMPs in animal models may be related to the delayed eruption of teeth. Mice deficient in membrane-type 1-MMP show delayed tooth eruption (10,14). MMP-8 is widely expressed in the periodontium during tooth eruption, and its expression may be coordinated with that of collagens types I and III (15).…”

“…For example, MT1-MMP is a membrane-bound matrix metalloproteinase, which has been shown to be involved in pericellular matrix digestion by activating a pro-metalloproteinase, presumably pro-MMP-2 (9). Deficiency of MT1-MMP results in inhibition of both root development and tooth eruption (10). Therefore, proper remodeling of the connective tissue is essential for tooth eruption (10).…”

“…Deficiency of MT1-MMP results in inhibition of both root development and tooth eruption (10). Therefore, proper remodeling of the connective tissue is essential for tooth eruption (10). Another example is the failure to digest collagen fiber, which results in an eruption disorder of the incisors in periostin knockout mice (11).…”

Proefschriften 25 jaar na dato 34. Collageenafbraak door fibroblasten en osteoclasten

“…Van het enzym collagenase werd aangetoond dat het niet betrokken was bij deze route van afbraak. Jaren later bleek dat een ander matrixmetalloproteïnase wel een rol speelt in dit proces, namelijk het membraangebonden matrixmetalloproteïnase-14 (Beertsen et al, 2002).…”