TY - JOUR
T1 - Chick limb bud mesodermal cell chondrogenesis
T2 - Inhibition by isoforms of platelet-derived growth factor and reversal by recombinant bone morphogenetic protein
AU - Chen, Ping
AU - Carrington, Jill L.
AU - Paralkar, Vishwas M.
AU - Pierce, Glenn F.
AU - Reddi, A. H.
N1 - Funding Information:
We thank Dr. Frank Luyten, Dr. Edith Wolff, and Dr. Noreen S. Cunningham for their constructive criticism of this manuscript. We thank Dr. W. Kenney, Dr. P. Hsieh, and Dr. A. Thomason for providing purified PDGF isoforms. This work was supported by the USUHS Protocol R070AN. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the DOD or the USUHS. The experiments reported herein were conducted according to the principles set forth in the "Guide for Care and Use of Laboratory Animals," Institute of Laboratory Animal Resources, National Research Council, DHEW, Publ. (NIH) 78-23.
PY - 1992/5
Y1 - 1992/5
N2 - Platelet-derived growth factor (PDGF) influences the proliferation and differentiation of a variety of cells. In this study, we have investigated the effect of PDGF isoforms on chondrogenesis by stage 24 chick limb bud mesoderm cells in culture. Synthesis of sulfated proteoglycans, an index of chondrogenesis, was inhibited by all three PDGF isoforms (PDGF-AA, PDGF-AB, and PDGF-BB). Application of PDGF isoforms during the first 2 days of culture, before the cells were overtly differentiating, resulted in decreased synthesis of sulfated proteoglycans. This was similar to when PDGF isoforms were present throughout the culture period. However, application of PDGF isoform during only the last 2 days of culture, did not inhibit cartilage matrix production. When chondrogenic and nonchondrogenic cells were separated from the cultures and replated, PDGF-AB and PDGF-BB inhibited the incorporation of sulfate by the chondrogenic cells. Recombinant bone morphogenetic protein 2B reversed the inhibitory effects of PDGF on sulfated proteoglycan synthesis and DNA synthesis. PDGF receptor binding analysis indicated that β-receptors were predominant receptors present on the chondrogenic and nonchondrogenic cells of the stage 24 mesoderm. PDGF isoforms increased thymidine incorporation by 48 h in both high and low density cultures. However, at later periods, cell proliferation was inhibited by PDGF-AA and PDGF-AB but not by PDGF-BB. PDGF acted as a bifunctional modulator of mesodermal cell proliferation and thus may regulate chondrogenesis during limb differentiation and morphogenesis.
AB - Platelet-derived growth factor (PDGF) influences the proliferation and differentiation of a variety of cells. In this study, we have investigated the effect of PDGF isoforms on chondrogenesis by stage 24 chick limb bud mesoderm cells in culture. Synthesis of sulfated proteoglycans, an index of chondrogenesis, was inhibited by all three PDGF isoforms (PDGF-AA, PDGF-AB, and PDGF-BB). Application of PDGF isoforms during the first 2 days of culture, before the cells were overtly differentiating, resulted in decreased synthesis of sulfated proteoglycans. This was similar to when PDGF isoforms were present throughout the culture period. However, application of PDGF isoform during only the last 2 days of culture, did not inhibit cartilage matrix production. When chondrogenic and nonchondrogenic cells were separated from the cultures and replated, PDGF-AB and PDGF-BB inhibited the incorporation of sulfate by the chondrogenic cells. Recombinant bone morphogenetic protein 2B reversed the inhibitory effects of PDGF on sulfated proteoglycan synthesis and DNA synthesis. PDGF receptor binding analysis indicated that β-receptors were predominant receptors present on the chondrogenic and nonchondrogenic cells of the stage 24 mesoderm. PDGF isoforms increased thymidine incorporation by 48 h in both high and low density cultures. However, at later periods, cell proliferation was inhibited by PDGF-AA and PDGF-AB but not by PDGF-BB. PDGF acted as a bifunctional modulator of mesodermal cell proliferation and thus may regulate chondrogenesis during limb differentiation and morphogenesis.
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U2 - 10.1016/S0014-4827(05)80078-3
DO - 10.1016/S0014-4827(05)80078-3
M3 - Article
C2 - 1314187
AN - SCOPUS:0026773806
SN - 0014-4827
VL - 200
SP - 110
EP - 117
JO - Experimental cell research
JF - Experimental cell research
IS - 1
ER -