Increased accumulation of superficial zone protein (SZF) in articular cartilage in response to bone morphogenetic protein-7 and growth factors

Afshin Khalafi, Thomas M. Schmid, Corey Neu, A Hari Reddi

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

The purpose of this study was to investigate the role of bone morphogenetic proteins (BMPs), such as BMP-7, growth factors, and cytokines, in the accumulation of superficial zone protein (SZP) in bovine articular cartilage. Calf superficial articular cartilage discs and chondrocytes were obtained for explant and monolayer culture systems, respectively. Dose- and time-dependent actions of BMP-7 on SZP accumulation were investigated in both explant and monolayer culture systems. In addition, actions of various morphogens and growth factors [BMP-2, BMP-4, fibroblast growth factor 2 (FGF-2), insulin-like growth factor 1(IGF-1), platelet-derived growth factor (PDGF), and transforming growth factor β (TGF-βl)], and cytokines [interleukin (IL)-lα, IL-1β, and tumor necrosis factor (TNF-α)] alone, and in combination with BMP-7, on SZP accumulation were investigated in monolayer culture systems. SZP accumulation was quantified in both the cartilage and the medium using SDS-PAGE and subsequent immunoblotting. In both explant and monolayer cultures, BMP-7 increased SZP accumulation in a dose- and time-dependent fashion (p < 0.05). Furthermore, SZP accumulation was significantly increased in monolayer cultures by FGF-2, IGF-1, PDGF, and TGF-β1 (p < 0.05). Both IL-lα and TNF-α significantly reduced SZP accumulation (p < 0.05). The inhibition of SZP accumulation by TNF-α was partially alleviated by concurrent treatment with BMP-7. The results of this investigation provide novel insights into the role of morphogens, especially BMP-7, growth factors, and cytokines in the accumulation of SZP in articular cartilage. This information has clinical implications because stimulation of SZP may ameliorate the pathology of joint function in arthritis. Furthermore, tissue engineering approaches to articular cartilage may depend on the optimal synthesis and assembly of SZP in the superficial zone to ensure functional tissue architecture.

Original languageEnglish (US)
Pages (from-to)293-303
Number of pages11
JournalJournal of Orthopaedic Research
Volume25
Issue number3
DOIs
StatePublished - Mar 2007

Keywords

  • Articular cartilage
  • Bone morphogenetic protein-7 (BMP-7)
  • Growth factors
  • Lubricin
  • Superficial zone protein (SZP)

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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