Inactivation of Lkb1 in postnatal chondrocytes leads to epiphyseal growth‐plate abnormalities and promotes enchondroma‐like formation

ABSTRACT Liver serine‐threonine kinase B1 (LKB1) is a tumor suppressor that has been linked to many types of tumors. However, the role of LKB1 in cartilaginous tumorigenesis is still poorly understood. In this study, we find that cartilage‐specific, tamoxifen‐inducible Lkb1 knockout results in multiple enchondroma‐like lesions adjacent to the disorganized growth plates. We showed that chondrocytes retain an immature status caused by loss of Lkb1 , which may lead to the dramatic expansion of growth‐plate cartilage and the formation of enchondroma‐like lesions. Additionally, increased mammalian target of rapamycin complex 1 (mTORC1) activity is observed in the Lkb1 conditional knockout (cKO) chondrocytes, and rapamycin (mTORC1 inhibitor) treatment significantly alleviates the expansion of growth‐plate cartilage and eliminates the enchondroma‐like lesions in Lkb1 cKO mice. Thus, our findings indicate that loss of Lkb1 leads to the expansion of chondrocytes and the formation of enchondroma‐like lesions during postnatal cartilage development, and that the up‐regulated mTORC1‐signaling pathway is implicated in this process. Our findings suggest that modulation of LKB1 and related signaling is a potential therapy in cartilaginous tumorigenesis.—Zhou, S., Li, Y., Qiao, L., Ge, Y., Huang, X., Gao, X., Ju, H., Wang, W., Zhang, J., Yan, J., Teng, H., Jiang, Q. Inactivation of Lkb1 in postnatal chondrocytes leads to epiphyseal growth‐plate abnormalities and promotes enchondroma‐like formation. FASEB J. 33,9476–9488 (2019). www.fasebj.org