Histone deacetylase 7 (Hdac7) suppresses chondrocyte proliferation and β-catenin activity during endochondral ossification.
Histone deacetylases (Hdacs) regulate endochondral ossification by suppressing gene transcription and modulating cellular responses to growth factors and cytokines. We previously showed that Hdac7 suppresses Runx2 activity and osteoblast differentiation. In this study, we examined the role of Hdac7 in postnatal chondrocytes. Hdac7 was highly expressed in proliferating cells within the growth plate. Postnatal tissue-specific ablation of Hdac7 with a tamoxifen-inducible collagen type 2a1-driven Cre recombinase increased proliferation and β-catenin levels in growth plate chondrocytes and expanded the proliferative zone. Similar results were obtained in primary chondrocyte cultures where Hdac7 was deleted with adenoviral-Cre. Hdac7 bound β-catenin in proliferating chondrocytes, but stimulation of chondrocyte maturation promoted the translocation of Hdac7 to the cytoplasm where it was degraded by the proteasome. As a result, β-catenin levels and transcription activity increased in the nucleus. These data demonstrate that Hdac7 suppresses proliferation and β-catenin activity in chondrocytes. Reducing Hdac7 levels in early chondrocytes may promote the expansion and regeneration of cartilage tissues.
From the Department of Orthopedic Surgery.
Elizabeth W
EW
Bradley
Mayo Graduate School and.
Lomeli R
LR
Carpio
Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
Eric N
EN
Olson
From the Department of Orthopedic Surgery, Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905 and westendorf.jennifer@mayo.edu.
Jennifer J
JJ
Westendorf
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D002356:Cartilage / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D006132:Growth Plate / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D006655:Histone Deacetylases / Q000172:deficiency / Q000235:genetics*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport; D059748:Proteolysis; D015398:Signal Transduction; D051176:beta Catenin / Q000819:agonists / Q000235:genetics* / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases; C543274:Hdac7 protein, mouse; D006655:Histone Deacetylases
ATDC5 Cells; Beta-catenin (β-catenin); Cartilage; Growth Plate; Histone Deacetylase (HDAC); Histone Deacetylase 7 (Hdac7); Insulin