Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation.
Proper longitudinal growth of long bones relies on the regulation of specific spatial patterns of chondrocyte proliferation and differentiation. We have studied the roles of two members of the Wnt family, Wnt5a and Wnt5b in long bone development. We show that Wnt5a is required for longitudinal skeletal outgrowth and that both Wnt5a and Wnt5b regulate the transition between different chondrocyte zones independently of the Indian hedgehog (Ihh)/parathyroid hormone-related peptide (PTHrP) negative feedback loop. We find that important cell cycle regulators such as cyclin D1 and p130, a member of the retinoblastoma family, exhibit complimentary expression patterns that correlate with the distinct proliferation and differentiation states of chondrocyte zones. Furthermore, we show that Wnt5a and Wnt5b appear to coordinate chondrocyte proliferation and differentiation by differentially regulating cyclin D1 and p130 expression, as well as chondrocyte-specific Col2a1 expression. Our data indicate that Wnt5a and Wnt5b control the pace of transitions between different chondrocyte zones.
Yang
Yingzi
Y
Genetic Disease Research Branch, National Human Genome Research Institute, National Institute of Health, Bethesda, MD 20892, USA. yyang@nhgri.nih.gov
Topol
Lilia
L
Lee
Heuijung
H
Wu
Jinling
J
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009024:Morphogenesis; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D055758:SOX9 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D006023:Glycoproteins; D053823:Hedgehog Proteins; D006609:High Mobility Group Proteins; D011518:Proto-Oncogene Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; C468567:Wnt5b protein, mouse