Differential regulation of lubricin/superficial zone protein by transforming growth factor beta/bone morphogenetic protein superfamily members in articular chondrocytes and synoviocytes.

OBJECTIVE To investigate the role of transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP) superfamily members on accumulation of superficial zone protein (SZP) in articular chondrocytes and synoviocytes. METHODS Chondrocytes and synoviocytes were isolated from articular cartilage and synovium from calf stifle joints and cultured as monolayers in serum-free chemically defined medium. Articular chondrocytes were isolated from 3 distinct zones of the cartilage: superficial, middle, and deep. Accumulation of SZP in the culture medium in response to various members of the TGFbeta/BMP superfamily was demonstrated by immunoblotting and quantified by enzyme-linked immunosorbent assay. RESULTS TGFbeta stimulated SZP accumulation in both superficial zone chondrocytes and synoviocytes. The 3 isoforms of TGFbeta elicited a similar dose response. Inhibition of TGFbeta receptor type I kinase by the specific inhibitor SB431542 abolished the TGFbeta-stimulated accumulation of SZP. BMPs up-regulated SZP accumulation in the superficial zone; however, the magnitude of the effects was not as great as was observed with TGFbeta. There was an additive action between TGFbeta and BMP on SZP accumulation. The response of synoviocytes to BMP was stronger than that of superficial zone chondrocytes. Activin up-regulated SZP accumulation in synoviocytes, but not in chondrocytes. CONCLUSION TGFbeta is a critical regulator of SZP accumulation in both superficial zone articular chondrocytes and synoviocytes. TGFbeta and BMP have an additive effect. Synoviocytes are more sensitive to BMP family members and activins than are superficial zone articular chondrocytes. Thus, regulation of SZP accumulation by TGFbeta /BMP superfamily members is regulated differently in articular chondrocytes and synoviocytes.

[1]  A. Reddi,et al.  Increased accumulation of superficial zone protein (SZP) in articular cartilage in response to bone morphogenetic protein‐7 and growth factors , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  G. Jay,et al.  Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen-induced arthritis. , 2007, Arthritis and rheumatism.

[3]  T. Desai,et al.  Expression of superficial zone protein in mandibular condyle cartilage. , 2006, Osteoarthritis and cartilage.

[4]  Margaret M. Smith,et al.  Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis , 2006, Arthritis research & therapy.

[5]  E. Vitters,et al.  Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity , 2005, Arthritis research & therapy.

[6]  G. Jay,et al.  Association of articular cartilage degradation and loss of boundary-lubricating ability of synovial fluid following injury and inflammatory arthritis. , 2005, Arthritis and rheumatism.

[7]  A. Reddi.  BMPs: from bone morphogenetic proteins to body morphogenetic proteins. , 2005, Cytokine & growth factor reviews.

[8]  F. Luyten,et al.  Bone morphogenetic protein signaling in joint homeostasis and disease. , 2005, Cytokine & growth factor reviews.

[9]  W. B. van den Berg,et al.  Elucidation of IL-1/TGF-beta interactions in mouse chondrocyte cell line by genome-wide gene expression. , 2005, Osteoarthritis and cartilage.

[10]  Véronique Lefebvre,et al.  The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. , 2005, The Journal of clinical investigation.

[11]  J. Buckwalter,et al.  Articular Cartilage and Osteoarthritis , 1954 .

[12]  A. Wallace,et al.  Proteomic Analysis of Articular Cartilage Shows Increased Type II Collagen Synthesis in Osteoarthritis and Expression of Inhibin βA (Activin A), a Regulatory Molecule for Chondrocytes* , 2004, Journal of Biological Chemistry.

[13]  S. Seité,et al.  Immunohistochemical analysis of transforming growth factor beta isoforms and their receptors in human cartilage from normal and osteoarthritic femoral heads , 2005, Rheumatology International.

[14]  A. Reddi,et al.  Cartilage morphogenetic proteins: role in joint development, homoeostasis, and regeneration , 2003, Annals of the rheumatic diseases.

[15]  G. Jay,et al.  Homology of lubricin and superficial zone protein (SZP): Products of megakaryocyte stimulating factor (MSF) gene expression by human synovial fibroblasts and articular chondrocytes localized to chromosome 1q25 , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[16]  K. Kuettner,et al.  Detection of superficial zone protein in human and animal body fluids by cross-species monoclonal antibodies specific to superficial zone protein. , 2001, Hybridoma.

[17]  Y. Nakamura,et al.  Isolation, characterization and mapping of the mouse and human PRG4 (proteoglycan 4) genes , 2000, Cytogenetic and Genome Research.

[18]  P. Robbins,et al.  Genetic enhancement of matrix synthesis by articular chondrocytes: comparison of different growth factor genes in the presence and absence of interleukin-1. , 2000, Arthritis and rheumatism.

[19]  G. Jay,et al.  Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts. , 2000, The Journal of rheumatology.

[20]  S. Schwartz,et al.  CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome , 1999, Nature Genetics.

[21]  K. Kuettner,et al.  Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte stimulating factor precursor and Is a multifunctional proteoglycan with potential growth-promoting, cytoprotective, and lubricating properties in cartilage metabolism. , 1999, Biochemical and biophysical research communications.

[22]  B. Schumacher,et al.  Immunodetection and partial cDNA sequence of the proteoglycan, superficial zone protein, synthesized by cells lining synovial joints , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  T. Yamamoto,et al.  Immunolocalization of transforming growth factor-beta s and type I and type II receptors in rat articular cartilage. , 1998, Anticancer research.

[24]  G. Jay,et al.  Comparison of the boundary-lubricating ability of bovine synovial fluid, lubricin, and Healon. , 1998, Journal of biomedical materials research.

[25]  M. Warman,et al.  The camptodactyly-arthropathy-coxa vara-pericarditis syndrome: clinical features and genetic mapping to human chromosome 1. , 1998, Arthritis and rheumatism.

[26]  A. Reddi,et al.  Role of morphogenetic proteins in skeletal tissue engineering and regeneration , 1998, Nature Biotechnology.

[27]  A. Freemont,et al.  Gene expression of matrix metalloproteinases 1, 3, and 9 by chondrocytes in osteoarthritic human knee articular cartilage is zone and grade specific , 1997, Annals of the rheumatic diseases.

[28]  A. Reddi,et al.  Regulation of the expression of the type‐II collagen gene in periosteum‐derived cells by three members of the transforming growth factor–β superfamily , 1997, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[29]  T. Aigner,et al.  Suppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage. , 1997, Arthritis and rheumatism.

[30]  D. Kingsley,et al.  Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family. , 1996, Development.

[31]  P. Atadja,et al.  Differential effects of transforming growth factor-β1 on the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in young and old human fibroblasts , 1996, Experimental Gerontology.

[32]  E. Thonar,et al.  The superficial layer of human articular cartilage is more susceptible to interleukin-1-induced damage than the deeper layers. , 1996, Arthritis and rheumatism.

[33]  J. Mort,et al.  Modulation of the catabolic effects of interleukin‐1β on human articular chondrocytes by transforming growth factor‐β , 1996 .

[34]  C. Rorabeck,et al.  Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration. , 1995, The Journal of clinical investigation.

[35]  J. T. Thomas,et al.  Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development. , 1994, The Journal of biological chemistry.

[36]  W. B. van den Berg,et al.  In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-beta 1: age-related differences. , 1994, Annals of the rheumatic diseases.

[37]  W. B. van den Berg,et al.  Transforming growth factor-beta 1 stimulates articular chondrocyte proteoglycan synthesis and induces osteophyte formation in the murine knee joint. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[38]  A Ratcliffe,et al.  Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis , 1994, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[39]  J. Block,et al.  A novel proteoglycan synthesized and secreted by chondrocytes of the superficial zone of articular cartilage. , 1994, Archives of biochemistry and biophysics.

[40]  N. Copeland,et al.  Limb alterations in brachypodism mice due to mutations in a new member of the TGFβ-superfamily , 1994, Nature.

[41]  F. Luyten,et al.  Recombinant bone morphogenetic protein-4, transforming growth factor-beta 1, and activin A enhance the cartilage phenotype of articular chondrocytes in vitro. , 1994, Experimental cell research.

[42]  W. B. van den Berg,et al.  Protection from interleukin 1 induced destruction of articular cartilage by transforming growth factor beta: studies in anatomically intact cartilage in vitro and in vivo. , 1993, Annals of the rheumatic diseases.

[43]  A. Mauviel,et al.  Transforming growth factor beta exerts opposite effects from interleukin-1 beta on cultured rabbit articular chondrocytes through reduction of interleukin-1 receptor expression. , 1993, Arthritis and rheumatism.

[44]  M E Bolander,et al.  Transforming Growth Factor b1 Stimulates Type I1 Collagen Expression in Cultured Periosteum-Derived Cells , 2022 .

[45]  G. Jay,et al.  Characterization of a bovine synovial fluid lubricating factor. II. Comparison with purified ocular and salivary mucin. , 1992, Connective tissue research.

[46]  G. Jay,et al.  Characterization of a bovine synovial fluid lubricating factor. I. Chemical, surface activity and lubricating properties. , 1992, Connective tissue research.

[47]  A. Harvey,et al.  Transforming growth factor-beta is a potent inhibitor of IL-1 induced protease activity and cartilage proteoglycan degradation. , 1988, Biochemical and biophysical research communications.

[48]  J. Heath,et al.  Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. , 1987, The EMBO journal.

[49]  F. Silver,et al.  The molecular structure and lubricating activity of lubricin isolated from bovine and human synovial fluids. , 1985, The Biochemical journal.

[50]  F H Silver,et al.  The molecular structure of lubricating glycoprotein-I, the boundary lubricant for articular cartilage. , 1981, The Journal of biological chemistry.

[51]  E. Radin,et al.  The lubricating activity of synovial fluid glycoproteins. , 1981, Arthritis and rheumatism.

[52]  D. Swann,et al.  The isolation and partial characterization of the major glycoprotein (LGP-I) from the articular lubricating fraction from bovine synovial fluid. , 1977, The Biochemical journal.