Regulation of anabolic and catabolic gene expression in normal and osteoarthritic adult human articular chondrocytes by osteogenic protein-1

Zhiyong Fan, Susan Chubinskaya, David C. Rueger, Brigitte Bau, Jochen Haag, Thomas Aigner

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Objective. Osteoarthritis is characterized by dramatic changes in chondrocyte metabolism including the overexpression of catabolic enzymes, but also a lack of anabolic activity. In this respect, osteogenic protein 1 (OP-1) appears to be one of the most potent anabolic factors of chondrocytes. In this study, we were interested in: (1) whether recombinant human OP-1 exerts its anabolic effects also on osteoarthritic chondrocytes, (2) whether OP-1 modulates the expression of catabolic genes, and (3) whether the BMP effects are related to the expression levels of its intracellular mediators (R- and 1-Smads). Methods. Chondrocytes were isolated from cartilage of either normal (n=5) or osteoarthritic (n=8) human knee joints and cultured in short-term high-density monolayer cultures with and without recombinant OP-1. RNA was isolated and analyzed for mRNA expression levels of anabolic (aggrecan, collagen type II), catabolic (MMP-1, -3, -13, ADAMTS-4), and intracellular signaling mediators (Smad 1, 4, 5, 6, 7, and 8) by quantitative online PCR. Results. After OP-1 stimulation, the anabolic genes were significantly up-regulated in osteoarthritic chondrocytes in comparison to normal chondrocytes. Neither in normal nor osteoarthritic chondrocytes were significant changes observed for the matrix degrading enzymes. Smads were also expressed in both normal and osteoarthritic cells at roughly the same level with and without stimulation with OP-1. Conclusion. Osteoarthritic chondrocytes are not hypo-responsive to anabolic stimulation by OP-1. Thus, human recombinant OP-1 could be a suitable anabolic activator of osteoarthritic chondrocytes. This might be of particular interest as chondrocytes themselves showed very low levels of OP-1 expression.

Original languageEnglish (US)
Pages (from-to)103-106
Number of pages4
JournalClinical and Experimental Rheumatology
Volume22
Issue number1
StatePublished - Jan 2004
Externally publishedYes

Keywords

  • Aggrecan
  • Bone morphogenetic protein
  • Chondrocytes
  • Collagen
  • MMP

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Regulation of anabolic and catabolic gene expression in normal and osteoarthritic adult human articular chondrocytes by osteogenic protein-1'. Together they form a unique fingerprint.

Cite this