Elevated expression of periostin in human osteoarthritic cartilage and its potential role in matrix degradation via matrix metalloproteinase‐13

Abstract

We investigated the role of periostin, an extracellular matrix protein, in the pathophysiology of osteoarthritis (OA). In OA, dysregulated gene expression and phenotypic changes in articular chondrocytes culminate in progressive loss of cartilage from the joint surface. The molecular mechanisms underlying this process are poorly understood. We examined periostin expression by immunohistochemical analysis of lesional and nonlesional cartilage from human and rodent OA knee cartilage. In addition, we used small interfering (si)RNA and adenovirus transduction of chondrocytes to knock down and upregulate periostin levels, respectively, and analyzed its effect on matrix metalloproteinase (MMP)-13, a disintegrin and MMP with thrombospondin motifs (ADAMTS)-4, and type II collagen expression. We found high periostin levels in human and rodent OA cartilage. Periostin increased MMP-13 expression dose [1-10 mg/ml (EC 50 0.5-1 mg/ml)] and time (24-72 h) dependently, significantly enhanced expression of ADAMTS4 mRNA, and promoted cartilage degeneration through collagen and proteoglycan degradation. Periostin induction of MMP-13 expression was inhibited by CCT031374 hydrobromide, an inhibitor of the canonical Wnt/b-catenin signaling pathway. In addition, siRNA-mediated knockdown of endogenous periostin blocked constitutive MMP-13 expression. These findings implicate periostin as a catabolic protein that promotes cartilage degeneration in OA by upregulating MMP-13 through canonical Wnt signaling.-Attur, M

Influence of Periostin on Synoviocytes in Knee Osteoarthritis

“…In addition, in some types of cells, periostin reportedly induces the expression of MMP family members (13,14). This induction and expression of matrix-degrading enzymes may function in tissues containing periostin, which is formed temporarily at the sites of damage to promote remodeling of the original tissue.…”

“…Periostin is considered to be an important structural mediator by balancing appropriate versus inappropriate tissue adaptation in response to insult/injury. Certain studies have shown that periostin is up-regulated in OA tissues (12)(13)(14). Previously, we reported that the periostin levels in synovial fluid were upregulated during the progression of OA in vivo, while in vitro experiments using human fibroblast-like synoviocytes suggested that addition of periostin mediated increased matrix metalloproteinase (MMP)-9 production (15).…”

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

“…Expression of periostin was previously shown to be elevated in OA cartilage compared to normal, and located in the pericellular ECM close to damaged areas of cartilage [46,47]. Periostin is able to increase expression of IL-6, IL-8, MMP-1,-3,-13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 by chondrocytes in vitro [46,47].…”

Matrix metalloproteinases in bone development and pathology: current knowledge and potential clinical utility

“…42 The expression and type II collagen degradation activity of the 48 kDa active MMP-13 can also be upregulated by ECM proteins such as type X collagen 43 and periostin. 44 There is now mounting evidence to suggest that increased MMP-13 activity is associated with articular cartilage degeneration and joint pathology typical of OA in animal models, and that MMP-13 expression is critical for OA disease progression. [43][44][45] Therefore, the development of pharmacologic inhibitors of MMP-13 in recent years seems to be an effective strategy to modify OA disease outcome.…”

“…44 There is now mounting evidence to suggest that increased MMP-13 activity is associated with articular cartilage degeneration and joint pathology typical of OA in animal models, and that MMP-13 expression is critical for OA disease progression. [43][44][45] Therefore, the development of pharmacologic inhibitors of MMP-13 in recent years seems to be an effective strategy to modify OA disease outcome. 46,47 In addition, a MMP-13 activity probe seems to be useful for in vivo imaging in OA disease diagnosis and differentiating disease severity.…”