scholarly journals 208 REDUCED IGF SIGNALING MAY BE RESPONSIBLE FOR THE DECLINE IN CARTILAGE MATRIX GENE EXPRESSION IN DEGENERATED AREAS WITHIN OSTEOARTHRITIC CARTILAGE

2011 ◽  
Vol 19 ◽  
pp. S102-S103
Author(s):  
N. Fukui ◽  
N. Tanaka ◽  
Y. Ikeda ◽  
T. Yamaguchi ◽  
Y. Miyamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cartilage Matrix ◽  
Osteoarthritic Cartilage ◽  
Matrix Gene ◽  
Igf Signaling

scholarly journals The attenuation of insulin-like growth factor signaling may be responsible for relative reduction in matrix synthesis in degenerated areas of osteoarthritic cartilage

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nobuho Tanaka ◽  
Hirotaka Tsuno ◽  
Satoru Ohashi ◽  
Mitsuyasu Iwasawa ◽  
Hiroshi Furukawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Analysis ◽  
Cartilage Explants ◽  
Relative Reduction ◽  
Growth Factor Signaling ◽  
Matrix Synthesis ◽  
Osteoarthritic Cartilage ◽  
Matrix Gene ◽  
Cultured Chondrocytes ◽  
Igf Signaling

Abstract Background In osteoarthritis (OA), cartilage matrix is lost gradually despite enhanced matrix synthesis by chondrocytes. This paradox may be explained, at least partly, by reduced chondrocyte anabolism in degenerated area of OA cartilage. However, to date, it is not known why chondrocyte anabolism is suppressed in those areas. Methods Cartilage was obtained from control knees and end-stage OA knees in macroscopically preserved areas and degenerated areas, and gene expression was analyzed in respective regions of cartilage using laser capture microdissection and qPCR. For the cartilage protein analysis, cartilage was obtained from preserved areas and degenerated areas of OA knees in pairs, and proteins were extracted using urea buffer. Protein concentrations were determined by Luminex and compared between the areas. Cartilage explants prepared from preserved areas and degenerated areas of OA knees were cultured in the presence or absence of an AKT inhibitor, and the gene expression was evaluated by qPCR. Finally, the expression of SP1 was evaluated in OA and control cartilage, and the significance of Sp1 on the expression of IGF1R and IRS1 was investigated in experiments using primary cultured chondrocytes. Results Within OA cartilage, the expression of IGF-1, IGF-2, IGF1R and IRS1 was reduced in degenerated areas compared to preserved areas, while the expression of all six IGF-binding protein genes examined was enhanced in the former areas. Consistent results were obtained by a protein analysis. In explant culture, the inhibition of AKT signaling abrogated the abundant matrix gene expression in the preserved areas over the degenerated areas, indicating that suppressed matrix synthesis in degenerated areas may be ascribed, at least partly, to attenuated IGF signaling. Within OA cartilage, the expression of Sp1 was considerably reduced in severely degenerated areas compared to preserved areas, which correlated well with the expression of IGF1R and IRS1. In experiments using primary cultured chondrocytes, the expression of IGF1R and IRS1 was enhanced by the induction of Sp1 expression and reduced by the suppression of Sp1 expression. Conclusions The results of this study suggest that attenuated IGF signaling may be responsible, at least partly, for the reduced matrix synthesis in degenerated areas of OA cartilage.

scholarly journals The attenuation of insulin-like growth factor signaling may be responsible for relative reduction in matrix synthesis in degenerated areas of osteoarthritic cartilage

2020 ◽  
Author(s):  
Nobuho Tanaka ◽  
Hirotaka Tsuno ◽  
Satoru Ohashi ◽  
Mitsuyasu Iwasawa ◽  
Hiroshi Furukawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Analysis ◽  
Cartilage Explants ◽  
Relative Reduction ◽  
Growth Factor Signaling ◽  
Matrix Synthesis ◽  
Osteoarthritic Cartilage ◽  
Matrix Gene ◽  
Cultured Chondrocytes ◽  
Igf Signaling

Abstract Background: In osteoarthritis (OA), cartilage matrix is lost gradually despite enhanced matrix synthesis by chondrocytes. This paradox may be explained, at least partly, by reduced chondrocyte anabolism in degenerated area of OA cartilage. However, to date, it is not known why chondrocyte anabolism is suppressed in those areas.Methods: Cartilage was obtained from control knees and end-stage OA knees in macroscopically preserved areas and degenerated areas, and gene expression was analyzed in respective regions of cartilage using laser capture microdissection and qPCR. For the cartilage protein analysis, cartilage was obtained from preserved areas and degenerated areas of OA knees in pairs, and proteins were extracted using urea buffer. Protein concentrations were determined by Luminex and compared between the areas. Cartilage explants prepared from preserved areas and degenerated areas of OA knees were cultured in the presence or absence of an AKT inhibitor, and the gene expression was evaluated by qPCR. Finally, the expression of SP1 was evaluated in OA and control cartilage, and the significance of Sp1 on the expression of IGF1R and IRS1 was investigated in experiments using primary cultured chondrocytes.Results: Within OA cartilage, the expression of IGF-1, IGF-2, IGF1R and IRS1 was reduced in degenerated areas compared to preserved areas, while the expression of all six IGF-binding protein genes examined was enhanced in the former areas. Consistent results were obtained by a protein analysis. In explant culture, the inhibition of AKT signaling abrogated the abundant matrix gene expression in the preserved areas over the degenerated areas, indicating that suppressed matrix synthesis in degenerated areas may be ascribed, at least partly, to attenuated IGF signaling. Within OA cartilage, the expression of Sp1 was considerably reduced in degenerated areas compared to preserved areas, which correlated well with the expression of IGF1R and IRS1. In experiments using primary cultured chondrocytes, the expression of IGF1R and IRS1 was enhanced by the induction of Sp1 expression and reduced by the suppression of Sp1 expression.Conclusions: The results of this study suggest that attenuated IGF signaling may be responsible, at least partly, for the reduced matrix synthesis in degenerated areas of OA cartilage.

scholarly journals Suppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage

1997 ◽  
Vol 40 (3) ◽  
pp. 562-569 ◽  
Author(s):  
T. Aigner ◽  
S. I. Vornehm ◽  
G. Zeiler ◽  
J. Dudhia ◽  
K. von der Mark ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cartilage Matrix ◽  
Osteoarthritic Cartilage ◽  
Matrix Gene

scholarly journals The attenuation of insulin-like growth factor signaling may be responsible for the relative reduction in matrix synthesis in degenerated areas of osteoarthritc cartilage

2021 ◽  
Author(s):  
Nobuho Tanaka ◽  
Hirotaka Tsuno ◽  
Satoru Ohashi ◽  
Mitsuyasu Iwasawa ◽  
Hiroshi Furukawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Analysis ◽  
Cartilage Explants ◽  
Relative Reduction ◽  
Growth Factor Signaling ◽  
Akt Inhibitor ◽  
Matrix Synthesis ◽  
Matrix Gene ◽  
Cultured Chondrocytes ◽  
Igf Signaling

Abstract Background: In osteoarthritis (OA), cartilage matrix is lost gradually despite enhanced matrix synthesis by chondrocytes. This paradox may be explained, at least partly, by reduced chondrocyte anabolism in degenerated area of OA cartilage. However, to date, it is not known why chondrocyte anabolism is suppressed in those areas.Methods: Cartilage was obtained from control knees and end-stage OA knees in macroscopically preserved areas and degenerated areas, and gene expression was analyzed in respective regions of cartilage using laser capture microdissection and qPCR. For the cartilage protein analysis, cartilage was obtained from preserved areas and degenerated areas of OA knees in pairs, and proteins were extracted using urea buffer. Protein concentrations were determined by Luminex and compared between the areas. Cartilage explants prepared from preserved areas and degenerated areas of OA knees were cultured in the presence or absence of an AKT inhibitor, and the gene expression was evaluated by qPCR. Finally, the expression of SP1 was evaluated in OA and control cartilage, and the significance of Sp1 on the expression of IGF1R and IRS1 was investigated in experiments using primary cultured chondrocytes.Results: Within OA cartilage, the expression of IGF-1, IGF-2, IGF1R and IRS1 was reduced in degenerated areas compared to preserved areas, while the expression of all six IGF-binding protein genes examined was enhanced in the former areas. Consistent results were obtained by a protein analysis. In explant culture, the inhibition of AKT signaling abrogated the abundant matrix gene expression in the preserved areas over the degenerated areas, indicating that suppressed matrix synthesis in degenerated areas may be ascribed, at least partly, to attenuated IGF signaling. Within OA cartilage, the expression of Sp1 was considerably reduced in severely degenerated areas compared to preserved areas, which correlated well with the expression of IGF1R and IRS1. In experiments using primary cultured chondrocytes, the expression of IGF1R and IRS1 was enhanced by the induction of Sp1 expression and reduced by the suppression of Sp1 expression. Conclusions: The results of this study suggest that attenuated IGF signaling may be responsible, at least partly, for the reduced matrix synthesis in degenerated areas of OA cartilage.

scholarly journals The Attenuation of Insulin-Like Growth Factor Signaling May Be Responsible for Relative Reduction in Matrix Synthesis in Degenerated Areas of Osteoarthritc Cartilage

2020 ◽  
Author(s):  
Nobuho Tanaka ◽  
Hirotaka Tsuno ◽  
Satoru Ohashi ◽  
Mitsuyasu Iwasawa ◽  
Hiroshi Furukawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Analysis ◽  
Cartilage Explants ◽  
Relative Reduction ◽  
Growth Factor Signaling ◽  
Akt Inhibitor ◽  
Matrix Synthesis ◽  
Matrix Gene ◽  
Cultured Chondrocytes ◽  
Igf Signaling

Abstract Background: In osteoarthritis (OA), cartilage matrix is lost gradually despite enhanced matrix synthesis by chondrocytes. This paradox may be explained, at least partly, by reduced chondrocyte anabolism in degenerated area of OA cartilage. However, to date, it is not known why chondrocyte anabolism is suppressed in those areas. Methods: Cartilage was obtained from control knees and end-stage OA knees in macroscopically preserved areas and degenerated areas, and gene expression was analyzed in respective regions of cartilage using laser capture microdissection and qPCR. For the cartilage protein analysis, cartilage was obtained from preserved areas and degenerated areas of OA knees in pairs, and proteins were extracted using urea buffer. Protein concentrations were determined by Luminex and compared between the areas. Cartilage explants prepared from preserved areas and degenerated areas of OA knees were cultured in the presence or absence of an AKT inhibitor, and the gene expression was evaluated by qPCR. Finally, the expression of SP1 was evaluated in OA and control cartilage, and the significance of Sp1 on the expression of IGF1R and IRS1 was investigated in experiments using primary cultured chondrocytes.Results: Within OA cartilage, the expression of IGF-1, IGF-2, IGF1R and IRS1 was reduced in degenerated areas compared to preserved areas, while the expression of all six IGF-binding protein genes examined was enhanced in the former areas. Consistent results were obtained by a protein analysis. In explant culture, the inhibition of AKT signaling abrogated the abundant matrix gene expression in the preserved areas over the degenerated areas, indicating that suppressed matrix synthesis in degenerated areas may be ascribed, at least partly, to attenuated IGF signaling. Within OA cartilage, the expression of Sp1 was considerably reduced in degenerated areas compared to preserved areas, which correlated well with the expression of IGF1R and IRS1. In experiments using primary cultured chondrocytes, the expression of IGF1R and IRS1 was enhanced by the induction of Sp1 expression and reduced by the suppression of Sp1 expression.Conclusions: The results of this study suggest that attenuated IGF signaling may be responsible, at least partly, for the reduced matrix synthesis in degenerated areas of OA cartilage.

IL-10 overexpression differentially affects cartilage matrix gene expression in response to TNF-α in human articular chondrocytes in vitro

Cytokine ◽  
2008 ◽  
Vol 44 (3) ◽  
pp. 377-385 ◽  
Author(s):  
R.D. Müller ◽  
T. John ◽  
B. Kohl ◽  
A. Oberholzer ◽  
T. Gust ◽  
...  
Keyword(s):  
Gene Expression ◽  
Articular Chondrocytes ◽  
Cartilage Matrix ◽  
Human Articular Chondrocytes ◽  
Matrix Gene ◽  
Tnf Α

scholarly journals P178 THE ROLE OF THE TRANSCRIPTION FACTOR C/EBP IN DOWN-REGULATION OF CARTILAGE MATRIX GENE EXPRESSION

2006 ◽  
Vol 14 ◽  
pp. S104-S105
Author(s):  
T. Imamura ◽  
C. Imamura ◽  
A. McAlinden ◽  
Y. Iwamoto ◽  
L.J. Sandell
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cartilage Matrix ◽  
Down Regulation ◽  
Matrix Gene ◽  
Factor C

scholarly journals Pharmacological inhibition of longevity regulator PAPP-A restrains mesenchymal stromal cell activity

2020 ◽  
Author(s):  
Mary Mohrin ◽  
Justin Liu ◽  
Jose Zavala-Solorio ◽  
Sakshi Bhargava ◽  
John Maxwell Trumble ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Cell Activity ◽  
Short Term Treatment ◽  
Matrix Gene ◽  
Age Related ◽  
Igf Signaling

AbstractReducing insulin-like growth factor (IGF) signaling is one of the best conserved and characterized mechanisms to extend longevity. Pregnancy associated plasma protein A (PAPP-A) is a secreted metalloprotease that increases IGF availability by cleaving IGF binding proteins. PAPP-A inhibition reduces local IGF signaling, limits the progression of multiple age-related diseases, and extends lifespan, but the mechanisms behind these pleiotropic effects remains unknown. Here, we developed and utilized a PAPP-A neutralizing antibody to discover that adulthood inhibition of this protease reduced collagen and extracellular matrix (ECM) gene expression in multiple tissues in mice. Using bone marrow to explore this effect, we identified mesenchymal stromal cells (MSCs) as the source of PAPP-A and primary responders to PAPP-A inhibition. Short-term treatment with anti-PAPP-A reduced IGF signaling in MSCs, altered MSC expression of collagen/ECM, and decreased MSC number. This affected MSC-dependent functions, decreasing myelopoiesis and osteogenesis. Our data demonstrate that PAPP-A inhibition reduces the activity and number of IGF-dependent mesenchymal progenitor cells and their differentiated progeny, and that this reduction leads to functional changes at the tissue level. MSC-like cells are present in virtually all tissues, and aberrant collagen and ECM production from mesenchymal cells drives aspects of aging and age-related diseases, thus this may be a mechanism by which PAPP-A deficiency enhances lifespan and healthspan.SummaryInhibition of PAPP-A, a regulator of IGF signaling, decreases multi-tissue collagen and extracellular matrix gene expression and modulates mesenchymal stromal cell activity in murine bone marrow.

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