PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue

Abstract

Objective. To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively. Methods. We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR. Results. Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes. Conclusions. PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.

Endogenous CCN family member WISP1 inhibits trauma-induced heterotopic ossification

“…Conversely, downregulated signaling pathways among Wisp1 -/cells included several pathways that negatively regulate chondrogenesis or promote cartilage matrix degradation, such as AMP-activated protein kinase (AMPK) signaling (Z score = -0.447) (36) and pigment epithelium-derived factor (PEDF) signaling (Z score = -0.447) (Supplemental Table 5) (37). Pathways with no change between Wisp1 +/+ and Wisp1 -/cells are shown in Supplemental Table 6.…”

Serpins in cartilage and osteoarthritis: what do we know?

“…Indeed, SerpinF1 has been reported to be increased in OA cartilage [45], and a recent study demonstrated that SerpinF1 deficiency reduces cartilage damage in an age-dependent manner in the murine monoiodoacetamide OA model, and overexpression in chondrocytes enhances cytokine-induced expression of catabolic MMPs [67]. In support of these observations, a different study demonstrated that stimulation of chondrocytes with recombinant SERPINF1 led to a catabolic phenotype and chondrocyte terminal differentiation [68].…”

Hip joint space width is causally related to hip osteoarthritis risk via distinct protective and susceptibility mechanisms: findings from a genome-wide association study meta-analysis

“…Pigment epithelium derived factor (PEDF) is the product of the EPC1 gene and is known to be anti-angiogenic. Previously PEDF has been shown to be preferentially expressed in OA cartilage contributing to OA pathogenesis by upregulating matrix degrading factors (38,39).…”

“…Pigment epithelium derived factor (PEDF) is the product of the EPC1 gene and is known to be anti-angiogenic. Previously PEDF has been shown to be preferentially expressed in OA cartilage contributing to OA pathogenesis by upregulating matrix degrading factors (38, 39). Whilst there was evidence of an association between rs34656141 with eQTL expression for AP3D1, DOT1L and AMH in fibroblasts these signals did not colocalise.…”