Transforming growth factors-beta 1 and beta 2 induce synthesis and accumulation of hyaluronate and chondroitin sulfate in vivo.
Subcutaneous implantation in rats of partially purified transforming growth factor-beta (TGF-beta) derived from bovine bone induced extensive development of connective tissue with associated edema. Subcutaneous injection of pure TGF-beta 1 or TGF-beta 2 also induced connective tissue deposition in mice and guinea pigs. Sustained release of TGF-beta 1 from mini-osmotic pumps implanted subcutaneously in mature guinea pigs promoted connective tissue deposition that encapsulated the pumps. Biochemical analyses of the connective tissue capsule demonstrated that TGF-beta 1 induced a dose-dependent accumulation of glycosaminoglycans (GAGs). The GAG/DNA ratio also increased as a function of the rate of TGF-beta 1 released, suggesting that the factor increased production of GAGs per cell. Cellulose acetate gel electrophoresis of the GAGs and hydrolysis with specific glycosidases revealed that the majority of GAGs consisted of hyaluronate and chondroitin sulfate. These results demonstrate that TGF-beta 1 and TGF-beta 2 stimulate the production of not only collagenous extracellular matrix components, but also dramatically increase the in vivo synthesis of hyaluronate and chondroitin sulfate.
Ogawa
Y
Y
Celtrix Laboratories, Collagen Corporation, Palo Alto, California 94303.
Sawamura
S J
SJ
Ksander
G A
GA
Armstrong
R M
RM
Pratt
B M
BM
McPherson
J M
JM
D000818:Animals; D002417:Cattle; D002807:Chondroitin / Q000031:analogs & derivatives*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D003238:Connective Tissue / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006168:Guinea Pigs; D006820:Hyaluronic Acid / Q000378:metabolism*; D015918:Infusion Pumps, Implantable; D009389:Neovascularization, Pathologic; D051381:Rats; D015291:Transforming Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*
D006025:Glycosaminoglycans; D015291:Transforming Growth Factors; D006820:Hyaluronic Acid; D002807:Chondroitin; D002809:Chondroitin Sulfates