The antimicrobial peptide KR-12 promotes the osteogenic differentiation of human bone marrow stem cells by stimulating BMP/SMAD signaling

Li, Hui; Zhang, Shutao; Nie, Bin’en; Du, Zhe; Long, Teng; Yue, Bing

doi:10.1039/c8ra00750k

Cited by 23 publications

(18 citation statements)

References 69 publications

(102 reference statements)

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“…The TGF-β pathway consists of extracellular ligands, transmembrane receptors, and intracellular regulatory factors. The receptor TGF-β activates Smads and enters the nucleus, thereby regulating its target genes (Hui et al, 2018); the MAPK signaling pathway involves MAPK/ERK/big MAP kinase 1 (BMK1)/stress activated protein (SAPK)/c-Jun N-terminal kinase (JNK)/P38 in five main ways (Lou et al, 2019;Jiang et al, 2018). The MAPK signaling pathway also plays an important role in the proliferation, differentiation and apoptosis of osteoblasts (Li et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and identification of circular RNAs promoting the osteogenic differentiation of human bone marrow mesenchymal stem cells on titanium treated by surface mechanical attrition

Zhu

Wang

et al. 2020

PeerJ

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Background To analyze and identify the circular RNAs (circRNAs) involved in promoting the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) on titanium by surface mechanical attrition treatment (SMAT). Methods The experimental material was SMAT titanium and the control material was annealed titanium. Cell Counting Kits-8 (CCK-8) was used to detect the proliferation of hBMSCs, and alkaline phosphatase (ALP) activity and alizarin red staining were used to detect the osteogenic differentiation of hBMSCs on the sample surfaces. The bioinformatics prediction software miwalk3.0 was used to construct competing endogenous RNA (ceRNA) networks by predicting circRNAs with osteogenesis-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The circRNAs located at the key positions in the networks were selected and analyzed by quantitative real-time PCR (QRT-PCR). Results Compared with annealed titanium, SMAT titanium could promote the proliferation and osteogenic differentiation of hBMSCs. The total number of predicted circRNAs was 51. Among these, 30 circRNAs and 8 miRNAs constituted 6 ceRNA networks. Circ-LTBP2 was selected for verification. QRT-PCR results showed that the expression levels of hsa_circ_0032599, hsa_circ_0032600 and hsa_circ_0032601 were upregulated in the experimental group compared with those in the control group; the differential expression of hsa_circ_0032600 was the most obvious and statistically significant, with a fold change (FC) = 4.25 ± 1.60, p-values (p) < 0.05.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and identification of circular RNAs promoting the osteogenic differentiation of human bone marrow mesenchymal stem cells on titanium treated by surface mechanical attrition

Zhu

Wang

et al. 2020

PeerJ

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“…Bormann et al reported high antimicrobial potency of some AMPs against bacteria both incorporated in a biofilm or internalized into cells with no harm to human osteoblasts [ 113 ]. Furthermore, Hui Li et al demonstrated that KR-12 - a fragment of human antimicrobial peptide cathelicidin LL-37 improves the osteogenic differentiation of human bone marrow mesenchymal stem cells via stimulating BMP/SMAD signaling [ 114 ]. Interestingly, Pavel Melicherˇcík et al reported that some antimicrobial peptides had lower minimum inhibitory concentrations (MICs) value than the two traditional antibiotics vancomycin and gentamincin but was found to be significantly more effective than those antibiotics when separately loaded into the calcium phosphate cement.…”

Section: Applications Of Amps In Some Infectious Diseasesmentioning

confidence: 99%

Antimicrobial peptides – Advances in development of therapeutic applications

2020

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The severe infection is becoming a significant health problem which threaten the lives of patients and the safety and economy of society. In the way of finding new strategy, antimicrobial peptides (AMPs) - an important part of host defense family, emerged with tremendous potential. Up to date, huge numbers of AMPs has been investigated from both natural and synthetic sources showing not only the ability to kill microbial pathogens but also propose other benefits such as wound healing, anti-tumor, immune modulation. In this review, we describe the involvements of AMPs in biological systems and discuss the opportunity in developing AMPs for clinical applications. In the detail, their properties in antibacterial activity is followed by their application in some infection diseases and cancer. The key discussions are the approaches to improve biological activities of AMPs either by modifying chemical structure or incorporating into delivery systems. The new applications and perspectives for the future of AMPs would open the new era of their development.

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“…Moreover, KR-12 does not lyse human red blood cells unlike LL-37, which produces a certain hemolytic effect (Jacob et al, 2013; Mishra et al, 2013). Our previous studies demonstrated KR-12 to promote HBMSC osteogenic differentiation while possessing good antibacterial properties (Li et al, 2018). As an analogue of KR-12, KR-12-a5 (KRIVKLILKWLR) has been reported to exhibit better antibacterial properties against clinically resistant bacteria while maintaining good biocompatibility.…”

Section: Introductionmentioning

confidence: 98%

“…Since KR-12 and several other antibacterial peptides have the ability to promote stem cell differentiation (Krasnodembskaya et al, 2010; Alcayaga-Miranda et al, 2017; Milhan et al, 2017; Li et al, 2018), KR-12-a5 may also have the potential to promote HBMSC osteogenic differentiation. Associated with the excellent anti-inflammatory properties of this small peptide, KR-12-a5-mediated regulation of osteogenesis can be expected under inflammatory conditions.…”

Section: Introductionmentioning

confidence: 99%

KR-12-a5 Reverses Adverse Effects of Lipopolysaccharides on HBMSC Osteogenic Differentiation by Influencing BMP/Smad and P38 MAPK Signaling Pathways

Zhang

Nie

et al. 2019

Front. Pharmacol.

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KR-12-a5 is an analogue of the antimicrobial peptide KR-12. Both of these two agents can play key effects in the treatment of infections such as osteomyelitis. Our previous work demonstrated that the osteogenic differentiation of human bone marrow mesenchymal stem cells (HBMSCs) can be enhanced by KR-12. The present study investigated if KR-12-a5 could reverse the adverse effects of lipopolysaccharides (LPS) on HBMSC osteogenesis and the involved molecular mechanisms. We observed the proliferation, cell cycle, and apoptosis of HBMSCs in the presence of KR-12-a5 by a cell counting kit-8 assay and flow cytometry. The osteogenic differentiation of HBMSCs was studied by alkaline phosphatase, Alizarin Red staining, and quantitative assays. Osteogenic differentiation marker levels were detected using real-time quantitative PCR analysis, which demonstrated that KR-12-a5 treatment reversed the inhibition of osteogenesis. Western blot analysis indicated that LPS-activated P38 mitogen-activated protein kinase (MAPK) signaling was inhibited and BMP/Smad pathway was reactivated after KR-12-a5 treatment under induced osteogenic conditions. Furthermore, flow cytometry results demonstrated that KR-12-a5 relieved LPS-induced oxidative stress. Combining the LPS-treated mouse model results, we proved that KR-12-a5 reversed the adverse effects of LPS on HBMSC osteogenic differentiation by influencing the BMP/Smad and P38 MAPK signaling pathways.

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The antimicrobial peptide KR-12 promotes the osteogenic differentiation of human bone marrow stem cells by stimulating BMP/SMAD signaling

Abstract: KR-12 is the smallest fragment of human antimicrobial peptide cathelicidin (LL-37), and could play key roles in the treatment of multiple infections, including osteomyelitis.

Cited by 23 publications

References 69 publications

Bioinformatics analysis and identification of circular RNAs promoting the osteogenic differentiation of human bone marrow mesenchymal stem cells on titanium treated by surface mechanical attrition

Bioinformatics analysis and identification of circular RNAs promoting the osteogenic differentiation of human bone marrow mesenchymal stem cells on titanium treated by surface mechanical attrition

Antimicrobial peptides – Advances in development of therapeutic applications

KR-12-a5 Reverses Adverse Effects of Lipopolysaccharides on HBMSC Osteogenic Differentiation by Influencing BMP/Smad and P38 MAPK Signaling Pathways

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