Increased accumulation of superficial zone protein (SZP) in articular cartilage in response to bone morphogenetic protein-7 and growth factors.
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 beta (TGF-beta1)], and cytokines [interleukin (IL)-1alpha, IL-1beta, and tumor necrosis factor (TNF-alpha)] 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-beta1 (p < 0.05). Both IL-1alpha and TNF-alpha significantly reduced SZP accumulation (p < 0.05). The inhibition of SZP accumulation by TNF-alpha 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.
Khalafi
Afshin
A
Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California-Davis, Sacramento, California 95817, USA. afshin.khalafi@ucdmc.ucdavis.edu
Schmid
Thomas M
TM
Neu
Corey
C
Reddi
A Hari
AH
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000378:metabolism*; D000099158:Proteoglycan 4
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C498836:PRG4 protein, Bos taurus; D000099158:Proteoglycan 4