A 15-amino acid C-terminal peptide of beta-defensin-3 inhibits bone resorption by inhibiting the osteoclast differentiation and disrupting podosome belt formation

Park, Ok-Jin; Kim, Jiseon; Ahn, Kyu Jeung; Lee, Jue Yeon; Park, Yoon-Jeong; Kum, Kee‐Yeon; Yun, Cheol‐Heui; Han, Seung Hyun

doi:10.1007/s00109-017-1589-2

Cited by 14 publications

(16 citation statements)

References 43 publications

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“…To overcome these limitations and identify the active peptide fragments within HBD3, the C-terminal HBD3 peptide was modified by substituting serine for cysteine residues, and shown to have retained its anti-microbial activity [42]. Recent reports showed that HBD3-C15 peptide could attenuate LPS-induced bone resorption, by disrupting podosome belt formation in osteoclasts and suppressing their differentiation [43]. In anti-inflammatory effect, HBD3-C15 did not affect upregulated TLR-2 level and its following signaling pathways in this study.…”

Section: Discussionmentioning

confidence: 99%

Synthetic Human β Defensin-3-C15 Peptide in Endodontics: Potential Therapeutic Agent in Streptococcus gordonii Lipoprotein-Stimulated Human Dental Pulp-Derived Cells

Yoo

Perinpanayagam

Lee³

et al. 2019

IJMS

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Human β defensin-3-C15, an epithelium-derived cationic peptide that has antibacterial/antifungal and immuno-regulatory properties, is getting attention as potential therapeutic agent in endodontics. This study aimed to investigate if synthetic human β defensin-3-C15 (HBD3-C15) peptides could inhibit inflammatory responses in human dental pulp cells (hDPCs), which had been induced by gram-positive endodontic pathogen. hDPC explant cultures were stimulated with Streptococcus gordonii lipoprotein extracts for 24 h to induce expression of pro-inflammatory mediators. The cells were then treated with either HBD3-C15 (50 μg/mL) or calcium hydroxide (CH, 100 μg/mL) as control for seven days, to assess their anti-inflammatory effects. Quantitative RT-PCR analyses and multiplex assays showed that S. gordonii lipoprotein induced the inflammatory reaction in hDPCs. There was a significant reduction of IL-8 and MCP-1 within 24 h of treatment with either CH or HBD3-C15 (p < 0.05), which was sustained over 1 week of treatment. Alleviation of inflammation in both medications was related to COX-2 expression and PGE2 secretion (p < 0.05), rather than TLR2 changes (p > 0.05). These findings demonstrate comparable effects of CH and HDB3-C15 as therapeutic agents for inflamed hDPCs.

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Section: Discussionmentioning

confidence: 99%

Synthetic Human β Defensin-3-C15 Peptide in Endodontics: Potential Therapeutic Agent in Streptococcus gordonii Lipoprotein-Stimulated Human Dental Pulp-Derived Cells

Yoo

Perinpanayagam

Lee³

et al. 2019

IJMS

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“…5-6), which subsequently leads to the attenuation of NFATc1 and c-Fos. NFATc1 and c-Fos are two crucial transcription factors that regulate osteoclast differentiation [31]. Furthermore, RANKL upregulated osteoclast-specific genes Cathepsin K and MMP9, which were reduced by ChondroT and its five constituent herbs (Fig.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of ChondroT and its constituent herbs on RANKL-induced osteoclastogenesis

Guo

Kim

Choi

et al. 2019

BMC Complement Altern Med

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BackgroundChondroT is a complex herbal medicine consisting of water extracts of Ostericum koreanum (Maxim.) Kitag., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis manshurica Rupr., and Phellodendron amurense Rupr. (6:4:4:4:3). Previous studies have reported that ChondroT possesses chondroprotective and anti-inflammatory, anti-osteoarthritic, and anti-hyperuricemic activities. The study is aim to demonstrate the effects of ChondroT and its five constituent herbs on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and the underlying mechanisms.MethodsOsteoclastogenesis was identified in bone marrow-derived macrophages (BMDMs) by tartrate-resistant acid phosphatase (TRAP) staining assay, actin ring formation assay and the bone resorption assay. For the molecular mechanisms, activation of RANKL-induced NF-κB and MAPK signaling pathways and the expression levels of osteoclast-specific proteins were investigated by Western blotting. Cell viability was assessed by MTT assay. Actin ring formation and NF-κB translocation were evaluated by immunostaining.ResultsChondroT and each of its constituent herbs significantly suppressed osteoclast differentiation dose dependently, and decreased actin ring formation as well as bone-resorbing capacity. Mechanistically, ChondroT and its constituent herbs downregulated the expressional levels of osteoclast-specific proteins such as NFATc1, c-Fos, Cathepsin K, and matrix metalloproteinase 9 (MMP9) by suppressing NF-κB translocation to nucleus and MAPKs phosphorylation at different levels. Compared to its five constituent herbs, ChondroT exhibited the best inhibitory efficiency against osteoclastogenesis.ConclusionsTaken together, ChondroT has anti-osteoclastogenesis properties by inhibiting NF-κB and MAPKs pathways. It could be considered as a potential therapeutic candidate for the treatment of osteoclast-related bone diseases.

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“…shown the potential to be a therapeutic agent for the inhibition of bone destruction (Park et al, 2017). Several synthesized cathelicidins from cattle (BMAP28), sheep (SMAP28 and SMAP29) and pigs (PMAP23) have shown broad-spectrum antimicrobial activities (Brogden et al, 2007).…”

Section: Artificial Antimicrobial Peptidesmentioning

confidence: 99%

The multifaceted roles of antimicrobial peptides in oral diseases

Niu

Yin

Mei

et al. 2021

Molecular Oral Microbiology

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Antimicrobial peptides are naturally occurring protein molecules with antibacterial, antiviral and/or antifungal activity. Some antimicrobial peptides kill microorganisms through direct binding with negatively charged microbial surfaces. This action disrupts the cytoplasmic membrane and leads to the leakage of the cytoplasm. In addition, they are involved in the innate immune response. Antimicrobial peptides play an important role in oral health, as natural antimicrobial peptides are the first line of host defence in response to microbial infection. The level of natural antimicrobial peptides increases during severe disease conditions and play a role in promoting the healing of oral tissues. However, they are insufficient for eliminating pathogenic micro-organisms. The variability of the oral environment can markedly reduce the effect of natural antimicrobial peptides. Thus, researchers are developing synthetic antimicrobial peptides with promising stability and biocompatibility. Synthetic antimicrobial peptides are a potential alternative to traditional antimicrobial therapy.Pertinent to oral diseases, the deregulation of antimicrobial peptides is involved in the pathogenesis of dental caries, periodontal disease, mucosal disease and oral cancer, where they can kill pathogenic microorganisms, promote tissue healing, serve as biomarkers and inhibit tumor cells. This narrative review provides an overview of the multifaceted roles of antimicrobial peptides in oral diseases.

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A 15-amino acid C-terminal peptide of beta-defensin-3 inhibits bone resorption by inhibiting the osteoclast differentiation and disrupting podosome belt formation

Abstract: HBD3-C15 inhibits osteoclast differentiation and bone resorption capacity. HBD3-C15 disrupts the podosome belt formation in osteoclasts. HBD3-C15 alleviates the bone loss by RANKL or A. actinomycetemcomitans LPS in vivo.

Cited by 14 publications

References 43 publications

Synthetic Human β Defensin-3-C15 Peptide in Endodontics: Potential Therapeutic Agent in Streptococcus gordonii Lipoprotein-Stimulated Human Dental Pulp-Derived Cells

Synthetic Human β Defensin-3-C15 Peptide in Endodontics: Potential Therapeutic Agent in Streptococcus gordonii Lipoprotein-Stimulated Human Dental Pulp-Derived Cells

Inhibitory effects of ChondroT and its constituent herbs on RANKL-induced osteoclastogenesis

The multifaceted roles of antimicrobial peptides in oral diseases

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