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

Takahiro Niikura, A Hari Reddi

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70 Citations (Scopus)

Abstract

Objective. To investigate the role of transforming growth factor β (TGFβ)/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 TGFβ/BMP superfamily was demonstrated by immunoblotting and quantified by enzyme-linked immunosorbent assay. Results. TGFβ stimulated SZP accumulation in both superficial zone chondrocytes and synoviocytes. The 3 isoforms of TGFβ elicited a similar dose response. Inhibition of TGFβ receptor type I kinase by the specific inhibitor SB431542 abolished the TGFβ-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 TGFβ. There was an additive action between TGFβ 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. TGFβ is a critical regulator of SZP accumulation in both superficial zone articular chondrocytes and synoviocytes. TGFβ 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 TGFβ /BMP superfamily members is regulated differently in articular chondrocytes and synoviocytes.

Original languageEnglish (US)
Pages (from-to)2312-2321
Number of pages10
JournalArthritis and Rheumatism
Volume56
Issue number7
DOIs
StatePublished - Jul 2007

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Bone Morphogenetic Proteins
Transforming Growth Factors
Chondrocytes
Joints
Proteins
Activins
Synoviocytes
lubricin
Stifle
Growth Factor Receptors
Synovial Membrane
Articular Cartilage
Immunoblotting
Cartilage
Culture Media
Protein Isoforms
Phosphotransferases
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

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title = "Differential regulation of lubricin/superficial zone protein by transforming growth factor β/bone morphogenetic protein superfamily members in articular chondrocytes and synoviocytes",
abstract = "Objective. To investigate the role of transforming growth factor β (TGFβ)/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 TGFβ/BMP superfamily was demonstrated by immunoblotting and quantified by enzyme-linked immunosorbent assay. Results. TGFβ stimulated SZP accumulation in both superficial zone chondrocytes and synoviocytes. The 3 isoforms of TGFβ elicited a similar dose response. Inhibition of TGFβ receptor type I kinase by the specific inhibitor SB431542 abolished the TGFβ-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 TGFβ. There was an additive action between TGFβ 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. TGFβ is a critical regulator of SZP accumulation in both superficial zone articular chondrocytes and synoviocytes. TGFβ 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 TGFβ /BMP superfamily members is regulated differently in articular chondrocytes and synoviocytes.",
author = "Takahiro Niikura and Reddi, {A Hari}",
year = "2007",
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doi = "10.1002/art.22659",
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pages = "2312--2321",
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T1 - Differential regulation of lubricin/superficial zone protein by transforming growth factor β/bone morphogenetic protein superfamily members in articular chondrocytes and synoviocytes

AU - Niikura, Takahiro

AU - Reddi, A Hari

PY - 2007/7

Y1 - 2007/7

N2 - Objective. To investigate the role of transforming growth factor β (TGFβ)/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 TGFβ/BMP superfamily was demonstrated by immunoblotting and quantified by enzyme-linked immunosorbent assay. Results. TGFβ stimulated SZP accumulation in both superficial zone chondrocytes and synoviocytes. The 3 isoforms of TGFβ elicited a similar dose response. Inhibition of TGFβ receptor type I kinase by the specific inhibitor SB431542 abolished the TGFβ-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 TGFβ. There was an additive action between TGFβ 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. TGFβ is a critical regulator of SZP accumulation in both superficial zone articular chondrocytes and synoviocytes. TGFβ 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 TGFβ /BMP superfamily members is regulated differently in articular chondrocytes and synoviocytes.

AB - Objective. To investigate the role of transforming growth factor β (TGFβ)/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 TGFβ/BMP superfamily was demonstrated by immunoblotting and quantified by enzyme-linked immunosorbent assay. Results. TGFβ stimulated SZP accumulation in both superficial zone chondrocytes and synoviocytes. The 3 isoforms of TGFβ elicited a similar dose response. Inhibition of TGFβ receptor type I kinase by the specific inhibitor SB431542 abolished the TGFβ-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 TGFβ. There was an additive action between TGFβ 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. TGFβ is a critical regulator of SZP accumulation in both superficial zone articular chondrocytes and synoviocytes. TGFβ 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 TGFβ /BMP superfamily members is regulated differently in articular chondrocytes and synoviocytes.

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