Hepatocyte growth factor/scatter factor modulates cell motility, proliferation, and proteoglycan synthesis of chondrocytes.
Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth factor that promotes proliferation, motility, and morphogenesis in epithelial cells. Recently the HGF receptor, c-met protooncogene product, has been shown to be expressed in developing limb buds (Sonnenberg, E., D. Meyer, M. Weidner, and C. Birchmeiyer, 1993. J. Cell Biol. 123: 223-235), suggesting that some populations of mesenchymal cells in limb buds respond to HGF/SF. To test the possibility that HGF/SF is involved in regulation of cartilage development, we isolated chondrocytes from knee joints and costal cartilages of 23-d embryonic and 4-wk-old rabbits, and analyzed the effects of HGF/SF on migration and proliferation of these cells. We found that HGF/SF stimulated migration of cultured articular chondrocytes but did not scatter limb mesenchymal fibroblasts or synovial fibroblasts in culture. HGF/SF also stimulated proliferation of chondrocytes; a maximum three-fold stimulation in DNA synthesis was observed at the concentration of 3 ng/ml of HGF/SF. Moreover, HGF/SF had the ability to enhance proteoglycan synthesis in chondrocytes. The responsiveness of chondrocytes to HGF/SF was also supported by the observation that they expressed the HGF/SF receptor. Addition of the neutralizing antibody to rat HGF/SF affected neither DNA synthesis nor proteoglycan synthesis in rat chondrocytes, suggesting a paracine mechanism of action of HGF/SF on these cells. In situ hybridization analysis showed that HGF/SF mRNA was restrictively expressed in the areas of future joint regions in developing limb buds and in the intercostal spaces of developing costal cartilages. These findings suggest that HGF/SF plays important roles in cartilage development through its multiple activities.
Takebayashi
T
T
Department of Oral Surgery, Okayama University Dental School, Japan.
Iwamoto
M
M
Jikko
A
A
Matsumura
T
T
Enomoto-Iwamoto
M
M
Myoukai
F
F
Koyama
E
E
Yamaai
T
T
Matsumoto
K
K
Nakamura
T
T
D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D011509:Proteoglycans; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor