Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis

Sun, Ping; Shi, Andi; Shen, Chenxi; Liu, Yi; Wu, Gang; Feng, Jianying

doi:10.1002/2211-5463.12906

Cited by 21 publications

(19 citation statements)

References 49 publications

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“…Collectively, our findings uncover a novel role for Histatin-1 in promoting osteoinduction, which paves new avenues to explore its effects in bone regeneration. It should be mentioned that, although the data shown here indicate a moderate osteoinductive effect of Histatin-1, as compared with standard osteoinductive factors, such as BMP-2 (Sun, Shi, Shen et al, 2020), this does not necessarily imply that the performance of Histatin-1 in bone regeneration is moderate or poor at the clinical level. This is because bone regeneration relies on multiple cellular and molecular phenomena regulated in a temporal and spatial manner (Marsell & Einhorn, 2011).…”

Section: F I G U R Econtrasting

confidence: 57%

“…Interestingly, a more recent study by Sun et al (Sun et al., 2020) showed that Histatin‐1 improves osteoinductive properties of BMP‐2 in a preclinical model. However, that study was conceived on the basis that Histatin‐1 is a proangiogenic factor, but not that the peptide itself was osteoinductive.…”

Section: Discussionmentioning

confidence: 99%

“…However, that study showed no alterations in ALP activity upon treatment with Histatin‐1 alone, which might be due to the result of brief exposure times or usage of a single cell line. Interestingly, a more recent study showed that Histatin‐1 increases the efficiency of bone morphogenetic protein‐2 (BMP‐2) in inducing ectopic bone formation in vivo (Sun, Shi, Shen et al., 2020), although the mechanisms underlying such effects have not been explored. Consequently, the basic question as to whether Histatin‐1 behaves as a factor that promotes osteogenic differentiation and other bone cell responses, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Histatin‐1 is a novel osteogenic factor that promotes bone cell adhesion, migration, and differentiation

Tôrres

Hernández

Mateluna

et al. 2021

J Tissue Eng Regen Med

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Histatin‐1 is a salivary antimicrobial peptide involved in the maintenance of enamel and oral mucosal homeostasis. Moreover, Histatin‐1 has been shown to promote re‐epithelialization in soft tissues, by stimulating cell adhesion and migration in oral and dermal keratinocytes, gingival and skin fibroblasts, endothelial cells and corneal epithelial cells. The broad‐spectrum activity of Histatin‐1 suggests that it behaves as a universal wound healing promoter, although this is far from being clear yet. Here, we report that Histatin‐1 is a novel osteogenic factor that promotes bone cell adhesion, migration, and differentiation. Specifically, Histatin‐1 promoted cell adhesion, spreading, and migration of SAOS‐2 cells and MC3T3‐E1 preosteoblasts in vitro, when placed on a fibronectin matrix. Besides, Histatin‐1 induced the expression of osteogenic genes, including osteocalcin, osteopontin, and Runx2, and increased both activity and protein levels of alkaline phosphatase. Furthermore, Histatin‐1 promoted mineralization in vitro, as it augmented the formation of calcium deposits in both SAOS‐2 and MC3T3‐E1 cells. Mechanistically, although Histatin‐1 failed to activate ERK1/2, FAK, and Akt, which are signaling proteins associated with osteogenic differentiation or cell migration, it triggered nuclear relocalization of β‐catenin. Strikingly, the effects of Histatin‐1 were recapitulated in cells that are nonosteogenically committed, since it promoted surface adhesion, migration, and the acquisition of osteogenic markers in primary mesenchymal cells derived from the apical papilla and dental pulp. Collectively, these observations indicate that Histatin‐1 is a novel osteogenic factor that promotes bone cell differentiation, surface adhesion and migration, as crucial events required for bone tissue regeneration.

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Section: F I G U R Econtrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Histatin‐1 is a novel osteogenic factor that promotes bone cell adhesion, migration, and differentiation

Tôrres

Hernández

Mateluna

et al. 2021

J Tissue Eng Regen Med

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“…All these data suggest that Hst1 does not enhance osteogenic differentiation, thus bearing no osteoinductivity. On the other hand, in our recent in vivo study, Hst1 significantly promotes angiogenesis and osteogenesis under the stimulation of BMP2 in an ectopic bone induction model (Sun P. et al, 2020). Such an effect of Hst1 on osteogenesis may be attributed to the stimulating effect of Hst1 on angiogenesis (Torres et al, 2017) that favors bone regeneration (Grosso et al, 2017).…”

Section: Discussionmentioning

confidence: 87%

Human Salivary Histatin-1 Promotes Osteogenic Cell Spreading on Both Bio-Inert Substrates and Titanium SLA Surfaces

Sun

Bolscher

et al. 2020

Front. Bioeng. Biotechnol.

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Promoting cell spreading is crucial to enhance bone healing and implant osteointegration. In this study, we investigated the stimulatory effect of human salivary histatin-1 (Hst-1) on the spreading of osteogenic cells in vitro as well as the potential signaling pathways involved. Osteogenic cells were seeded on bio-inert glass slides with or without the presence of Hst1 in dose-dependent or time-course assays. 1 scrambled and 6 truncated Hst1 variants were also evaluated. Cell spreading was analyzed using a well-established point-counting method. Fluorescent microscopy was adopted to examine the cellular uptake of fluorescently labeled Hst1 (F-Hst1) and also the cell spreading on sandblasted and acid etched titanium surfaces. Signaling inhibitors, such as U0126, SB203580, and pertussis toxin (PTx) were used to identify the potential role of extracellular-signal-regulated kinase, p38 and G protein-coupled receptor pathways, respectively. After 60 min incubation, Hst1 significantly promoted the spreading of osteogenic cells with an optimal concentration of 10 µM, while truncated and scrambled Hst1 did not. F-Hst1 was taken up and localized in the vicinity of the nuclei. U0126 and SB2030580, but not PTx, inhibited the effect of Hst1. 10 µM Hst1 significantly promoted the spreading of osteogenic cells on both bio-inert substrates and titanium SLA surfaces, which involved ERK and p38 signaling. Human salivary histatin-1 might be a promising peptide to enhance bone healing and implant osteointegration in clinic.

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“…Among natural antimicrobial peptides, hBDs are expressed in oral bone (Warnke et al, 2006) (Warnke et al, 2013). In addition, hBDs and histatin-1 promoted bone regeneration and prevented infection (Lee et al, 2018;Peng et al, 2020;Sun et al, 2020).…”

Section: Natural 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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Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis

Cited by 21 publications

References 49 publications

Histatin‐1 is a novel osteogenic factor that promotes bone cell adhesion, migration, and differentiation

Histatin‐1 is a novel osteogenic factor that promotes bone cell adhesion, migration, and differentiation

Human Salivary Histatin-1 Promotes Osteogenic Cell Spreading on Both Bio-Inert Substrates and Titanium SLA Surfaces

The multifaceted roles of antimicrobial peptides in oral diseases

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