The role of lamin A/C in mesenchymal stem cell differentiation
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REVIEW
The role of lamin A/C in mesenchymal stem cell differentiation Bo Zhang 1,2 & Yang Yang 1,3 & Reziwan Keyimu 1,2 & Jin Hao 4 & Zhihe Zhao 1,2 & Rui Ye 1,2 Received: 15 December 2017 / Accepted: 21 January 2019 # University of Navarra 2019
Abstract Lamin A/C is the major architectural protein of cell nucleus in charge of the nuclear mechanosensing. By integrating extracellular mechanical and biochemical signals, lamin A/C regulates multiple intracellular events including mesenchymal stem cell (MSC) fate determination. Herein, we review the recent findings about the effects and mechanisms of lamin A/C in governing MSC lineage commitment, with a special focus on osteogenesis and adipogenesis. Better understanding of MSC differentiation regulated by lamin A/C could provide insights into pathogenesis of age-related osteoporosis. Keywords Lamin A/C . Mesenchymal stem cells . Osteogenesis . Adipogenesis
Abbreviations ECM Extracellular matrix HGPS Hutchinson-Gilford progeria syndrome KASH Klarsicht/ANC-1/Syne homology LINC Linkers of nucleoskeleton and cytoskeleton MKL1 Megakaryoblastic leukemia 1 MSC Mesenchymal stem cell RA Retinoic acid RAR Retinoic acid receptors RARE RA-responsive elements SRF Serum response factor SUN Sad1/UNC-84 YAP Yes-associated protein TAZ transcriptional co-activators with PDZ-binding motif Bo Zhang and Yang Yang contributed equally to this work. * Zhihe Zhao [email protected] * Rui Ye [email protected] 1
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
2
Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
3
Department of General Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China
4
Program in Biological Sciences in Dental Medicine, Harvard School of Dental Medicine, Boston, MA, USA
Introduction Age-related bone loss, increasing the fracture risk of the elderly individuals, has become increasingly prevalent and has caused enormous health care costs. Approximately 13% of the individuals would experience osteoporosis in China [64], and about 20% of the patients suffering from osteoporotic fractures died in 1 year because of related complications [11]. The disease has been found to be characterized by decreasing bone formation and increasing adipose tissue infiltration in bone marrow, which is the result of the switch of mesenchymal stem cell (MSC) differentiation from osteogenesis to adipogenesis [19]. However, the mechanisms of the switch remain unclear. One possible mediator of MSC fate is lamin A/C, a kind of lamin protein in the nucleus contributing to nuclear mechanics [13] and mechanotransduction [50]. Lamin A/C levels decreased in osteoblasts during aging [16], indicating participation of lamin A/C in the development of senile skeletal phenotypes. In vivo evidence showed that mutation of LMNA caused Hutchinson-Gilford progeria syndrome (HGPS), the disease characterized by age-related bo
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