title: Osteogenic growth peptide promotes osteogenic differentiation of mesenchymal stem cells mediated by LncRNA AK141205-induced upregulation of CXCL13.
abstract: The aim of present study was to characterize long non-coding RNA (lncRNA) AK141205 as a cellular regulator of osteogenic differentiation of mice mesenchymal stem cells (MSCs) towards osteogenic growth peptide (OGP) stimulation. Mice MSCs cells were isolated, transfected with si-AK141205, pcDNA-AK141205 or control, and stimulated with OGP. The AK141205, CXC chemokine ligand-13 (CXCL13), and osteogenic differentiation-associated parameters were determined by western blotting or quantitative RT-PCR. To determine the role of AK141205/CXCL13 in SMCs osteogenic differentiation, SMCs subjected to co-transfection of pcDNA-AK141205 and si-CXCL13 or si-AK141205 and pcDNA-CXCL13, and were submitted for osteogenic differentiation-associated parameters analyses. The results showed that stimulation of SMCs with OGP induced upregulation of both AK141205 and CXCL13, and osteogenic differentiation of MSCs. Transfection of si-AK141205 partly suppressed OGP-induced formation of calcium salt nodules, alkaline phosphatase (ALP) activity and osteogenic differentiation-associated gene expression, suggesting key regulatory role of AK141205. Analysis of CXCL13 expression in SMCs(pcDNA-AK141205) revealed that AK141205 positively promoted CXCL13 expression via acetylation of H4 histone in the promoter region. This signal transduction was demonstrated to be essential for OGP-induced osteogenic differentiation of MSCs through osteogenic differentiation analysis in simultaneously AK141205/CXCL13 controlled SMCs. In summary, we report a completely novel role of AK141205/CXCL13 as a regulator of OGP-induced osteogenic differentiation of SMCs. Our finding provides a potential therapeutic targeting of AK141205 for enhancing disease-treatment effect of SMCs.
authors: Department of Orthopedic Surgery, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng 252000, China.
authors: Haiqing
authors: H
authors: Li
authors: Department of Orthopedic Surgery, Liaocheng Hospital of Traditional Chinese Medicine, Liaocheng 252000, China.
authors: Zhonghe
authors: Z
authors: Zhang
authors: Department of Orthopedic Surgery, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng 252000, China. Electronic address: zhiqiangchch@163.com.
authors: Zhiqiang
authors: Z
authors: Chen
authors: Department of Ultrasound, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng 252000, China. Electronic address: dongddzhang@163.com.
authors: Dongdong
authors: D
authors: Zhang
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D010012:Osteogenesis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D054382:Chemokine CXCL13; D050659:Core Binding Factor Alpha 1 Subunit; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D062085:RNA, Long Noncoding; C074533:osteogenic growth peptide
keywords: AK141205; Alkaline phosphatase (ALP) activity; Mesenchymal stem cells; Osteogenic growth peptide; Runx2