Lamin A/C-Dependent Translocation of Megakaryoblastic Leukemia-1 and β-Catenin in Cyclic Strain-Induced Osteogenesis

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 12; p. 3518
• Main Authors: Khan, Asmat Ullah, Qu, Rongmei, Yang, Yuchao, Fan, Tingyu, Peng, Yan, Sun, Bing, Qiu, Xianshuai, Wu, Shutong, Wang, Zetong, Zhou, Zhitao, Khan, Muhammad Akram, Dai, Jingxing, Ouyang, Jun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.12.2021; MDPI
• Subjects: Alkaline phosphatase; Animals; beta Catenin - metabolism; Cbfa-1 protein; Cell Line; Core Binding Factor Alpha 1 Subunit - metabolism; Cytoplasm; Fibroblasts; Filaments; Fluorescence; Gene expression; Humans; Intermediate filaments; Kinases; lamin A/C (LMNA); Lamin Type A - metabolism; Lamins; Leukemia; Mechanical stimuli; mechanical strain; megakaryoblastic leukemia-1 (MKL1); Mice; Mutation; Osteogenesis; Osteoporosis; Protein expression; Proteins; Stem cells; Stress, Mechanical; Trans-Activators; β-Catenin; β-catenin; mechanical strain; osteogenesis; megakaryoblastic leukemia-1 (MKL1); lamin A/C (LMNA)
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10123518

Lamins are intermediate filaments that play a crucial role in sensing mechanical strain in the nucleus of cells. β-catenin and megakaryoblastic leukemia-1 (MKL1) are critical signaling molecules that need to be translocated to the nucleus for their transcription in response to mechanical strain that induces osteogenesis. However, the exact molecular mechanism behind the translocation of these molecules has not been fully investigated. This study used 10% cyclic strain to induce osteogenesis in the murine osteoblast precursor cell line (MC3T3). The translocation of β-catenin and MKL1 was studied by performing knockdown and overexpression of lamin A/C (LMNA). Cyclic strain increased the expression of osteogenic markers such as alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and enhanced ALP staining after seven days of incubation. Resultantly, MKL1 and β-catenin were translocated in the nucleus from the cytoplasm during the stress-induced osteogenic process. Knockdown of LMNA decreased the accumulation of MKL1 and β-catenin in the nucleus, whereas overexpression of LMNA increased the translocation of these molecules. In conclusion, our study indicates that both MKL1 and β-catenin molecules are dependent on the expression of LMNA during strain-induced osteogenesis.