Abstract
The aim of the present study is to investigate the effects of BMP-7 released from polylactide microspheres on the appearance of various catabolic and inflammatory cytokines secreted by osteoarthritic chondrocytes cultivated in a collagen gel. Articular chondrocytes of 15 patients suffering from osteoarthritis are transferred to a collagen type-I gel. Additionally, BMP-7 encapsulated into polylactide microspheres (50 ng BMP-7/mL gel) is added. After 14 days, gene expression and protein appearance of various genes involved in matrix turnover and inflammation are investigated by immunohistochemical staining and RT-PCR and compared to untreated controls. TNF-α, MMP-13, IL-6, IL-1β, and VEGF gene expressions are decreased in the treatment group. In contrast, BMP-7-induced matrix synthesis is not affected, leaving collagen type-II (Col-II) gene expression to be elevated, while collagen type-I (Col-I) is decreased. In summary, controlled release of low concentrated BMP-7 from polylactide microspheres leads to a decrease in gene expression of the investigated inflammation and matrix degradation markers whereas matrix synthesis is induced.
MeSH terms
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Base Sequence
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Biomarkers / metabolism
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Bone Morphogenetic Protein 7 / administration & dosage*
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Cell Culture Techniques
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Chondrocytes / drug effects*
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Chondrocytes / metabolism*
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Chondrocytes / pathology
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Collagen Type I / genetics
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Collagen Type I / metabolism
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Collagen Type II / genetics
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Collagen Type II / metabolism
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Cytokines / genetics
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Cytokines / metabolism
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Delayed-Action Preparations
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Gene Expression / drug effects
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Humans
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Inflammation Mediators / metabolism*
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Matrix Metalloproteinase 13 / genetics
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Matrix Metalloproteinase 13 / metabolism
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Microspheres
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Osteoarthritis / genetics
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Osteoarthritis / metabolism*
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Osteoarthritis / pathology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Proteins / administration & dosage
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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BMP7 protein, human
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Biomarkers
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Bone Morphogenetic Protein 7
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Collagen Type I
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Collagen Type II
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Cytokines
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Delayed-Action Preparations
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IL6 protein, human
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Inflammation Mediators
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Interleukin-1beta
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Interleukin-6
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RNA, Messenger
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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MMP13 protein, human
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Matrix Metalloproteinase 13