Schminke B., Frese J., Bode C., Goldring M.B., Miosge N.
American Society for Investigative Pathology, 2015
This is an investigation of cartilage tissue and isolated chondrocytes in three-dimensional culture obtained from patients with late-stage knee OA and nidogen-2 knockout mice. Chondrogenic progenitor cells (CPCs) produced high levels of laminin-a1, laminin-a5, and nidogen-2 in their pericellular matrix, and laminin-a1 enhanced collagen type II and reduced collagen type I expression by cultured CPCs. Nidogen-2 increased SOX9 gene expression. This study reveals that the influence of the pericellular matrix on CPCs is important for the expression of the major regulator transcription factors, SOX9 and RUNX2. Our novel findings that laminins and nidogen-2 drive CPCs toward chondrogenesis may help in the elucidation of new treatment strategies for cartilage tissue regeneration. In summary, the expression of nidogen-2 and laminin is increased in human OA cartilage, and they act as chondrogenic regulators, especially for CPCs. Laminin also promotes chondrogenesis, enhancing collagen type II, COMP, and aggrecan expression, and down-regulating collagen type I. Therefore, these findings on laminin and nidogen-2 may aid in the elucidation of new treatment options, especially for tissue regeneration.