TRIM37 is highly expressed during mitosis in CHON-002 chondrocytes cell line and is regulated by miR-223

Multiple molecular disorders can affect mechanisms regulating proliferation and differentiation of growth plate chondrocytes. Mutations in the TRIM37 gene cause the Mulibrey nanism, a heritable growth disorder. Since chondrocytes are instrumental in long bone growth that is deficient in nanism, we hypothesized that TRIM37 defect could contribute to dysregulation of the chondrocyte cell cycle. Western blotting, confocal microscopy and imaging flow cytometry determined TRIM37 expression in CHON-002 cell lineage. We showed that TRIM37 is expressed during mitosis of chondrocytes and directly impacted their proliferation. During the chondrocyte cell cycle, TRIM37 was present in both nucleus and cytoplasm. During M phase we observed an increase of the TRIM37-Tubulin co-localization in comparison with G1, S and G2 phases. TRIM37 knock down inhibited proliferation, together with cell cycle anomalies and increased autophagy, while overexpression accordingly enhanced cell proliferation. We demonstrated that microRNA-223 directly targets TRIM37, and suggest that miR223 regulates TRIM37 gene expression during the cell cycle. In summary, our results give clues to explain why TRIM37 deficiency in chondrocytes impacts bone growth. Modulating TRIM37 using miR-223 could be an approach to increase chondrogenesis.