Sulfoxide stimulation of chondrogenesis in limb mesenchyme is accompanied by an increase in type II collagen enhancer activity.
We have utilized a modification of the limb bud mesenchyme micromass culture system to screen compounds that might stimulate chondrogenesis. Two compounds in the sulfoxide family (methylphenylsulfoxide and p-chlorophenyl methyl sulfoxide) were stimulatory at 10(-2) M and 10(-3) M, respectively; whereas other sulfoxides and organic solvents were not active at these concentrations. In addition, specific growth factors (basic FGF, IGF-I, IGF-II) were not chondroinductive at concentrations that are active in other cell systems. Both sulfoxide compounds stimulated cartilage nodule formation, [35S]sulfate incorporation, and activity of the regulatory sequences of the collagen II gene. In contrast, transforming growth factor beta-1 (10 ng/ml) stimulated sulfate incorporation but produced only a diffuse deposition of cartilage matrix and reduced the ability of the cells to utilize the regulatory sequences of the collagen II gene. The sulfoxides appear to promote the differentiation of limb bud cells to chondrocytes and thus exhibit chondroinductive activity.
Horton
W E
WE
National Institute on Aging, Gerontology Research Center, Baltimore, Maryland 21224.
Higginbotham
J D
JD
D000818:Animals; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000187:drug effects* / Q000235:genetics; D005121:Extremities / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D013454:Sulfoxides / Q000494:pharmacology*; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D013431:Sulfates; D013454:Sulfoxides; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003094:Collagen