NITEGE-Expression in Meniscal Matrix (apjot)
No marker reflecting the pathobiology of meniscal degeneration (MD) is established so far. NITEGE is a hexapeptide fragments produced when aggrecan is cleaved. Methods. In vitro IL-1 exposition of bovine menisci (n = 4) caused extracellular NITEGE deposits detected by immunofluorescence. A retrospective immunohistochemical analysis of (n = 60) patients after meniscectomy for NITEGE deposits was performed. MD was graded as follows: no/little (grade 0/1), medium (grade 2) or severe (grade 3). Results. NITEGE deposits in areas of degeneration were demonstrated in 55% of the patients with grade 2 or 3 MD (PPV & specificity 100%), while no extracellular NITEGE deposits in the menisci with grade 0 or 1 MD could be detected. Age correlated with NITEGE deposits (r = 0.46) and grade of MD (r = 0.48). NITEGEpositive cell density and size were significantly higher close to a tear (p < 0, 001). Interpretation. Extracellular NITEGE deposits may be regarded as markers of medium and severe MD and might be used in diagnostic histopathology.
The major meniscal functions are to distribute stress across the knee during weight bearing, provide shock absorption, serve as secondary joint stabilizers, facilitate joint gliding, and protect the joint margins (Brindle et al. ). Meniscal degeneration (MD) goes along with a loss of the meniscal function described above contributing to a higher incidence of tears. It is a common disorder that has been morphologically described long ago; however studies concerning the pathogenesis are scarce. All we know today about MD is almost exclusively derived from conventional HE-, Alcian-Blue or vG-staining, while only few immunohistochemical markers for MD are available (Dankof et al. ).
Histomorphologically three different variants of MD have been described: calcification, acellular hyaline degeneration and mucoid or myxoid degeneration (FerrerRoca et al. [9,10]). Several reasons for developing MD have been considered: trauma (Romanini et al. , Smillie ) malnutrition, vascular disturbance (Burri , Krenn et al. , McDevitt et al. ). Some studies demonstrated MD to be a physiological state of age (Konn [ ¨ 15], Slany ). All conflicting concepts can be consolidated by considering the basic distinction between primary (Slany ) and secondary MD. Primary MD is defined as all morphological alterations in cellular and fibrillar meniscal components that are stronger than usual age-related changes. Secondary MD is seen in degenerative, inflammatory, posttraumatic, and metabolic joint diseases (Andreesen , Aufdermaur ). The microstructural characteristics of the menisci dictate their mechanical properties. The menisci are composed of 70% water and 30% organic matter. Collagen (Type I) constitutes 75% of the organic matter, while roughly 8% to 13% of the remaining dry matter consists of proteoglycans (Adams et al. , Brindle et al. ). They make up only 1% of the wet weight of the meniscus but contribute significantly to its material properties (Fithian et al. ). Degradation of one of the components of the extracellular meniscal matrix either collagens or proteoglycans is resulting in degeneration of the meniscus. Aggrecan is the main proteoglycan of the extracellular meniscal matrix (Hoberg et al. , Verdonk et al. ), and NITEGE is one of the G1-fragments produced when the proteoglycan aggrecan is cleaved by aggrecanase activity. NITEGE is a hexapeptide consisting of Asn-Ile-Thr-GluGly-Glu, hence the name. It has been suspected to be a marker for MD, however there has been no study so far that investigated the NITEGE distribution in degenerated human meniscal tissue.
We therefore studied by in vitro analysis of bovine meniscal fragments whether NITEGE may be expressed after stressing IL-1 exposition. Secondly, we carried out immunohistochemical analysis of human menisci for NITEGE expression and correlated NITEGE patterns with different grades of MD to see if NITEGE is of use as a pathogenetic marker for MD.
Journal of Orthopedic and trauma.
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