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 XXXX in STR/ort @entity19 .

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