OBJECTIVE: To map aggrecan cleavage by matrix metalloproteinases (MMPs) and aggrecanases in normal @entity19 tibial articular cartilage (CBA strain) and in the development of @entity571 ( @entity571 ) in the STR/ort @entity19 and to assess the influence of sex hormone status on these conditions in gonadectomized STR/ort @entity19 . METHODS: The distributions of neoepitopes of aggrecan generated by MMP (VDIPEN) and aggrecanase (NITEGE) cleavage were investigated by immunohistochemistry. RESULTS: VDIPEN neoepitope was detected mainly in the pericellular matrix of deep-zone chondrocytes in normal tibial cartilage from STR/ort and CBA @entity19 . In early @entity571 , VDIPEN immunostaining also localized to the pericellular matrix of chondrocytes at the site of the lesion. With increasing severity of @entity75 , VDIPEN immunostaining was also detected in the interterritorial matrix, close to the site of the lesion. In contrast, NITEGE mapped most strongly to the pericellular matrix of upper-zone chondrocytes in normal tibial cartilage. As with VDIPEN, NITEGE was strongly expressed in the pericellular matrix at the site of early @entity75 . With advancing @entity571 , NITEGE colocalized with VDIPEN in both the pericellular and interterritorial matrices of chondrocytes adjacent to @entity75 and in those of the deep zones. Hormone status did not appear to influence the development of @entity571 or the distribution of aggrecan neoepitopes in STR/ort @entity19 . CONCLUSION: MMP- and aggrecanase-generated neoepitopes map predominantly to different regions in normal @entity19 tibial cartilage. However, both groups of enzymes generate increased amounts of neoepitopes in pericellular and interterritorial matrix adjacent to histopathologic lesions of @entity571 . Aggrecan degradation and the development of @entity571 appear to be independent of sex hormone status in this model.

Matrix metalloproteinases and aggrecanases cleave aggrecan in different zones of normal cartilage but colocalize in the development of @entity75 in STR/ort XXXX .

@entity19 :: ('10090', 'Species') :: ['mice', 'mouse', 'murine'] @entity75 :: ('MESH:D001927', 'Disease') :: ['OA lesions'] @entity571 :: ('MESH:D010003', 'Disease') :: ['spontaneous osteoarthritis', 'OA']
@entity19 :: (10090,Species) :: ['mice']
