Regional differences in chondrocyte metabolism in osteoarthritis: A detailed analysis by laser capture microdissection

Abstract

Objective. To determine the change in metabolic activity of chondrocytes in osteoarthritic (OA) cartilage, considering regional difference and degree of cartilage degeneration.Methods. OA cartilage was obtained from knee joints with end-stage OA, at both macroscopically intact areas and areas with various degrees of cartilage degeneration. Control cartilage was obtained from agematched donors. Using laser capture microdissection, cartilage samples were separated into superficial, middle, and deep zones, and gene expression was compared quantitatively in the respective zones between OA and control cartilage.Results. In OA cartilage, gene expression changed markedly with the site. The expression of cartilage matrix genes was highly enhanced in macroscopically intact areas, but the enhancement was less obvious in the degenerated areas, especially in the upper regions. In contrast, in those regions, the expression of type III collagen and fibronectin was most enhanced, suggesting that chondrocytes underwent a phenotypic change there. Within OA cartilage, the expression of cartilage matrix genes was significantly correlated with SOX9 expression, but not with SOX5 or SOX6 expression. In OA cartilage, the strongest correlation was observed between the expression of type III collagen and fibronectin, suggesting the presence of a certain link(s) between their expression.Conclusion. The results of this study revealed a comprehensive view of the metabolic change of the chondrocytes in OA cartilage. The change of gene expression profile was most obvious in the upper region of the degenerated cartilage. The altered gene expression at that region may be responsible for the loss of cartilage matrix associated with OA.

Effects of low molecular weight hyaluronan combined with carprofen on canine osteoarthritis articular chondrocytes and cartilage explants in vitro

“…The COL2A1 gene provides instructions to produce the pro-alpha 1 (II) chain and encode the alpha-1 chain of type II collagen in the cartilage matrix. Several previous studies have investigated the relationship between COL2A1 gene expression and osteoarthritis (Fukui et al 2008;Mu et al 2009;Brew et al 2010). AGG encodes a large chondroitin sulfate proteoglycan which acts as a core protein that interacts with glycosaminoglycans and HA (Jayasuriya and Chen 2012).…”

αvβ5 Integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes

“…Chondrocyte dedifferentiation is characterized by the loss of chondrocyte phenotype, which is represented by the decline in expression of type II procollagen and aggrecan, which are 2 major matrix genes expressed by chondrocytes (10,29,30). To examine the involvement of the respective integrins in dedifferentiation, we suppressed the expression of the 11 dominant integrins listed above in chondrocytes one by one by RNAi and observed whether any increase (or recovery) occurred in the expression of type II procollagen and aggrecan.…”

Cartilage biology, pathology, and repair

“…In the upper zones of OA articular cartilage, expression of COL2AI is significantly suppressed while collagen type III and fibronectin is upregulated during the progression of matrix destruction [50]. Thus, chondrocytes yield a different kind of matrix structure, which is more susceptible to erosion and to loss of proteoglycans [50,51]. In contrast, the middle and deeper zones exhibit a normal metabolism, producing predominantly cartilaginous ECM molecules [30].…”