Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family

Little is known about the regulatory signals involved in tendon and ligament formation, and this lack of understanding has hindered attempts to develop biologically based therapies for tendon and ligament repair. Here we report that growth and differentiation factors (GDFs) 5, 6, and 7, members of t...

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Bibliographic Details
Published in:The Journal of clinical investigation 1997-07, Vol.100 (2), p.321-330
Main Authors: Wolfman, N M, Hattersley, G, Cox, K, Celeste, A J, Nelson, R, Yamaji, N, Dube, J L, DiBlasio-Smith, E, Nove, J, Song, J J, Wozney, J M, Rosen, V
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins - metabolism
Bone Morphogenetic Proteins - pharmacology
Cell Differentiation - physiology
Cloning, Molecular
Decorin
Elastin - analysis
Extracellular Matrix Proteins
Gene Expression Regulation, Developmental - genetics
Growth Differentiation Factor 5
Growth Differentiation Factor 6
Growth Differentiation Factors
Growth Substances - genetics
Growth Substances - pharmacology
Histocytochemistry
Humans
In Situ Hybridization
Joints - growth & development
Ligaments - cytology
Ligaments - growth & development
Ligaments - transplantation
Mice
Molecular Sequence Data
Proteoglycans - analysis
Rats
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
RNA, Messenger - analysis
RNA, Messenger - genetics
Tendons - cytology
Tendons - growth & development
Tendons - transplantation
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - pharmacology
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Summary:Little is known about the regulatory signals involved in tendon and ligament formation, and this lack of understanding has hindered attempts to develop biologically based therapies for tendon and ligament repair. Here we report that growth and differentiation factors (GDFs) 5, 6, and 7, members of the TGF-beta gene superfamily that are most related to the bone morphogenetic proteins, induce neotendon/ligament formation when implanted at ectopic sites in vivo. Analysis of tissue induced by GDF-5, 6, or 7, containing implants by currently available morphological and molecular criteria used to characterize tendon and ligament, adds further evidence to the idea that these GDFs act as signaling molecules during embryonic tendon/ligament formation. In addition, comparative in situ localizations of the GDF-5, 6, and 7 mRNAs suggest that these molecules are important regulatory components of synovial joint morphogenesis.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci119537