Dataset Information

LMP1 regulates periodontal ligament progenitor cell proliferation and differentiation.

ABSTRACT: LMP1 is an intracellular scaffold protein that contains a PDZ domain and three LIM domains. LMP1 has multiple functions including regulating mesenchymal stem cell (MSC) osteogenesis. Gene delivery of LMP1 induces bone formation in vivo in heterotopic and orthotopic sites. However, little is known about the physiological function and gene regulatory mechanisms of LMP1 in MSCs at the molecular level. Periodontal ligament (PDL) cells are a unique progenitor cell population that can differentiate into multiple cell types, including osteoblasts, adipocytes, or chondrocytes. This study sought to determine the physiological function and gene regulatory mechanisms of LMP1 in PDL cells at the molecular level. We show that LMP1 is upregulated in early stage of PDL cell osteogenic differentiation. Stable gene knockdown of LMP1 by shRNA inhibits DNA synthesis and corresponding cell proliferation in PDL cells, and further leads to decreased mineralization in vitro. Overexpression of LMP1 increases cell proliferation, and PDZ and ww-interacting domains are not sufficient to mediate this effect. Further, we found that in PDL cells, LMP1 is a downstream target gene of TGF-beta1 that is an early signal critical in preosteoblast proliferation and differentiation. TGF-beta1 stimulates PDL cell proliferation, however, this effect is compromised when LMP1 is knocked down. We further identified that the activation of TAK1-JNK/p38 kinase cascade is involved in the LMP1 gene regulation by TGF-beta1. We conclude that LMP1 is a downstream gene of TGF-beta1, involved in PDL cell proliferation. Our findings advance the understanding of the physiological function of LMP1 and define a regulatory mechanism of LMP1 in PDL progenitor cells and other MSCs.

SUBMITTER: Lin Z

PROVIDER: S-EPMC2891403 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LMP1 regulates periodontal ligament progenitor cell proliferation and differentiation.

Lin Zhao Z Navarro Valeria Pontelli VP Kempeinen Kathryn M KM Franco Lea M LM Jin Qiming Q Sugai James V JV Giannobile William V WV

Bone 20100327 1

LMP1 is an intracellular scaffold protein that contains a PDZ domain and three LIM domains. LMP1 has multiple functions including regulating mesenchymal stem cell (MSC) osteogenesis. Gene delivery of LMP1 induces bone formation in vivo in heterotopic and orthotopic sites. However, little is known about the physiological function and gene regulatory mechanisms of LMP1 in MSCs at the molecular level. Periodontal ligament (PDL) cells are a unique progenitor cell population that can differentiate in ...[more]

PMID: 20348040

Similar Datasets

Project description:Periodontitis is a common chronic inflammatory oral disease. The objective of periodontal treatment is to control infection whilst regenerating damaged periodontal tissue. The present study aimed to determine the potential effects of pterostilbene (PTE), a representative stilbene compound, on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs). Different concentrations (1, 5, 10 and 20 µM) of PTE were applied to hPDLSCs, after which Cell Counting Kit-8 and western blotting assays were performed to examine the protein levels of Ki67, PCNA, p-IκBα, IκBα, Bcl-2, Bax, cleaved caspase3. The effect of PTE on the release of inflammatory factors, including IL-1β, IL-6 and IL-10 was assessed by RT-qPCR. The apoptosis of TNF-α-induced hPDLSCs was evaluated by TUNEL assay and western blotting. Additionally, the role of PTE in hPDLSC mineralization was evaluated using alizarin red staining. The expression levels of mineralization indices, including RUNX2 and ALP were subsequently determined using western blotting. Subsequently, the target of PTE was predicted using TargetNet database and AutoDock v4.2 software and verified using western blotting. The results of the present study revealed that PTE promoted the proliferation of hPDLSCs in a concentration-dependent manner. Furthermore, PTE treatment decreased the release of inflammatory factors and alleviated the apoptosis of TNF-α-induced hPDLSCs. PTE was also demonstrated to promote the formation of mineral nodules in TNF-α-induced hPDLSCs. The Targetnet database, along with molecular docking, indicated that histone deacetylases (HDACs) were the probable targets of PTE upstream of regulating periodontitis. The results of western blotting implied that TNF-α significantly increased expression levels of HDAC2, 4, 6 and 8, whilst PTE treatment markedly decreased HDAC4, 6 and 8 expression in a concentration-dependent manner compared with the TNF-α group, which further confirmed these conclusions. In summary, results of the present study revealed that PTE promoted TNF-α-induced hPDLSC proliferation and differentiation, whilst alleviating inflammation and apoptosis. PTE also inhibited the expression of HDACs, which may be involved in the mechanism of periodontitis.

Dataset Information

LMP1 regulates periodontal ligament progenitor cell proliferation and differentiation.

Publications

LMP1 regulates periodontal ligament progenitor cell proliferation and differentiation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets