Biomaterial Database

Transforming growth factor-beta and insulin-like growth factor-1 restore proteoglycan metabolism of bovine articular cartilage after depletion by retinoic acid. 1994

T I Morales

Bone Research Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.

Previous studies showed that retinoic acid is a powerful resorbing agent for articular cartilage at physiological doses (10(-8) to 10(-10) M); the possible role of individual cytokines in the reversal of this effect is now explored in bovine articular cartilage organ cultures. Seven days of treatment with the retinoid under serum-free conditions, at 1 x 10(-8) M, led to a suppression of proteoglycan synthesis of 90 +/- 5% (n = 6; n = cultures from different animals; mean +/- SD) and to a net loss of 64 +/- 14% (n = 6). Removal of the retinoid from the feeding medium did not significantly increase proteoglycan synthesis nor diminish the further loss of proteoglycans. Thus, transforming growth factor-beta (TGF-beta) and insulin-like growth factor-1 (IGF-1), cytokines which independently maintain proteoglycan homeostasis (Morales and Roberts, 1988, J. Biol. Chem. 263, 828; and Luyten et al., 1988, Arch. Biochem. Biophys. 267, 416), were tested. TGF-beta (10 ng/ml) or IGF-1 (10 ng/ml) added for 7 days to serum-free medium following retinoic acid treatment led to recoveries of proteoglycan synthesis of 74 +/- 24% (n = 12) and 69 +/- 18% (n = 12), respectively, as compared to controls switched from serum-free conditions to corresponding cytokine treatments. TGF-beta + IGF-1 restored activity to 95 +/- 17% (n = 12) of controls. TGF-beta s 1-3 exhibited identical responses in control and experimental cultures. IGF-2 replaced IGF-1, but a fourfold higher concentration was required; insulin also had IGF-1-like effects, but even at 500 ng/ml it was 25% less effective than IGF-1. In contrast to the cultures switched from retinoic acid treatment to serum-free conditions, the cultures switched to IGF-1, TGF-beta, or IGF-1 + TGF-beta were stabilized from further proteoglycan loss by the treatment; after 1 week, tissue levels were 97 +/- 19, 96 +/- 22, and 114 +/- 15% (n = 6), respectively, compared to the content before switching. Measurements of catabolism were in agreement with these observations. It is proposed that retinoic acid, TGF-beta, and IGF-1 are parts of an endogenous system involved in the reversible modulation of proteoglycan homeostasis in articular cartilage.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D007334	Insulin-Like Growth Factor I	A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.	IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D011509	Proteoglycans	Glycoproteins which have a very high polysaccharide content.	Proteoglycan,Proteoglycan Type H
D002358	Cartilage, Articular	A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.	Articular Cartilage,Articular Cartilages,Cartilages, Articular
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002809	Chondroitin Sulfates	Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.	Chondroitin 4-Sulfate,Chondroitin 6-Sulfate,Chondroitin Sulfate A,Chondroitin Sulfate C,Blutal,Chondroitin 4-Sulfate, Aluminum Salt,Chondroitin 4-Sulfate, Potassium Salt,Chondroitin 6-Sulfate, Potassium Salt,Chondroitin 6-Sulfate, Sodium Salt,Chondroitin Sulfate,Chondroitin Sulfate 4-Sulfate, Sodium Salt,Chondroitin Sulfate, Calcium Salt,Chondroitin Sulfate, Iron (+3) Salt,Chondroitin Sulfate, Iron Salt,Chondroitin Sulfate, Potassium Salt,Chondroitin Sulfate, Sodium Salt,Chondroitin Sulfate, Zinc Salt,Chonsurid,Sodium Chondroitin Sulfate,Translagen,Chondroitin 4 Sulfate,Chondroitin 4 Sulfate, Aluminum Salt,Chondroitin 4 Sulfate, Potassium Salt,Chondroitin 6 Sulfate,Chondroitin 6 Sulfate, Potassium Salt,Chondroitin 6 Sulfate, Sodium Salt,Chondroitin Sulfate 4 Sulfate, Sodium Salt,Chondroitin Sulfate, Sodium,Sulfate, Chondroitin,Sulfate, Sodium Chondroitin,Sulfates, Chondroitin
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005109	Extracellular Matrix	A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.	Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D014176	Protein Biosynthesis	The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.	Genetic Translation,Peptide Biosynthesis, Ribosomal,Protein Translation,Translation, Genetic,Protein Biosynthesis, Ribosomal,Protein Synthesis, Ribosomal,Ribosomal Peptide Biosynthesis,mRNA Translation,Biosynthesis, Protein,Biosynthesis, Ribosomal Peptide,Biosynthesis, Ribosomal Protein,Genetic Translations,Ribosomal Protein Biosynthesis,Ribosomal Protein Synthesis,Synthesis, Ribosomal Protein,Translation, Protein,Translation, mRNA,mRNA Translations