Histone Deacetylase 7 (Hdac7) Suppresses Chondrocyte Proliferation and β-Catenin Activity during Endochondral Ossification

Background: Hdac7 is a transcriptional co-repressor in skeletal tissues, but its role in chondrocytes is undefined. Results: Proteasomal degradation reduced Hdac7 levels during chondrogenic maturation and conditional deletion of Hdac7 in chondrocytes increased proliferation and -catenin levels. Conclusion: Hdac7 degradation enhances -catenin transcriptional activity in growth plate chondrocytes. Significance: Suppressing Hdac7 levels increases chondrocyte proliferation and promotes cartilage formation and regeneration. 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 -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 -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, -catenin levels and transcription activity increased in the nucleus. These data demonstrate that Hdac7 suppresses proliferation and -catenin activity in chondrocytes. Reducing Hdac7 levels in early chondrocytes may promote the expansion and regeneration of cartilage tissues.