Dentinogenic effects of extracted dentin matrix components digested with matrix metalloproteinases

Okamoto, Masakazu; Takahashi, Yusuke; Komichi, Shungo; Cooper, Paul R.; Hayashi, Mikako

doi:10.1038/s41598-018-29112-3

Cited by 41 publications

(53 citation statements)

References 73 publications

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“…Then, the pulp capping procedure was performed as described previously (Okamoto et al . ,b). Briefly, after anaesthetizing the animals, the experimental teeth were cleaned and isolated with a rubber dam (Heraeus Kulzer, South Bend, IN, USA) with a custom‐made rubber dam clamp (YDM, Tokyo, Japan) to perform sterile treatment (Fig.…”

Section: Methodsmentioning

confidence: 99%

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Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

et al. 2019

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Aim To evaluate the dentinogenetic effects of tissue inhibitor of metalloprotease (TIMP1) on human pulp cells in vitro and rat pulp tissue in vivo. Methodology The effect of TIMP1 on pulp cell functions related to hard tissue formation as part of the wound healing process (i.e. biocompatibility, proliferation, differentiation and mineralized nodule formation) was evaluated in vitro and using a direct pulp capping experimental animal model in vivo. The effects of different‐sized cavity preparations on hard tissue formation induced by ProRoot MTA at 2 weeks were evaluated using micro‐computed tomography (micro‐CT). Tertiary dentine formation quality and quantity after pulp capping using TIMP1, ProRoot MTA and phosphate‐buffered saline (PBS) was also evaluated after 4 weeks using micro‐CT in term of dentine volume (DV), dentine mineral density (DVD) and histological analysis. The data were evaluated by Student's t‐test, one‐way ANOVA with Tukey's post hoc test, the Kruskal–Wallis test or the Steel–Dwass test. P values < 0.05 were considered statistically significant. Results TIMP1 significantly stimulated dental pulp stem cell proliferation, differentiation, and mineralization and was more biocompatible compared with the PBS control (P < 0.05). In the pulp capping model, the amount of tertiary dentine that formed was directly proportional to the size of the pulp exposure; greater amounts of tertiary dentine were observed in pulps with larger exposures after 2 weeks. 4‐week samples of TIMP1 and ProRoot MTA had similar characteristics, but both sample significantly induced tertiary dentine formation beneath the cavity compared with PBS (P < 0.05) under standardized cavity preparations. Conclusions TIMP1 has an important role in pulpal wound healing, which makes it a potential biological pulp capping material and candidate molecule for regenerative endodontic therapy.

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Section: Methodsmentioning

confidence: 99%

“…Tertiary dentine was quantified as previously described (Okamoto et al . ,b). The criteria used for histological evaluation are shown in Table .…”

Section: Methodsmentioning

confidence: 99%

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

et al. 2019

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“…Indeed, a problem with pulpal biomarkers and MMPs in particular is that they are not just destructive in nature; they also increase the bioactivity and reparative capacity of DMCs by further digesting the extracts (Okamoto et al . ). DMCs contain multiple bioactive components, including GFs, chemokines, cytokines, MMPs and bioactive proteins (Smith et al .…”

Section: Reviewmentioning

confidence: 97%

“…Selected matrix metalloproteinases (MMPs), a family of tissue proteases, contained with the DMCs will propagate the breakdown of dentine matrix (Mazzoni et al 2015), whilst releasing other bioactive molecules that migrate down the dentinal tubules Deep caries and pulp exposure Bjørndal et al and stimulate tertiary dentine formation and other pulpal reparative processes (Finkelman et al 1990, B egue-Kirn et al 1992. Indeed, a problem with pulpal biomarkers and MMPs in particular is that they are not just destructive in nature; they also increase the bioactivity and reparative capacity of DMCs by further digesting the extracts (Okamoto et al 2018). DMCs contain multiple bioactive components, including GFs, chemokines, cytokines, MMPs and bioactive proteins , which modulate a range of processes critical to repair, including chemotaxis (Smith et al 2012, Galler et al 2016a, angiogenesis (Roberts-Clark & Smith 2000), mineralization (Tomson et al 2013), stem cell (SC) recruitment (Fayazi et al 2017) and neurogenesis (Marquardt et al 2015).…”

Section: Role Of Dentine In Repairmentioning

confidence: 99%

Management of deep caries and the exposed pulp

et al. 2019

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Caries prevalence remains high throughout the world, with the burden of disease increasingly affecting older and socially disadvantaged groups in Western cultures. If left untreated, caries will advance through dentine stimulating pulpitis and eventually pulp infection and necrosis; however, if conservatively managed, pulpal recovery occurs even in deep carious lesions. Traditionally, deep caries management was destructive with nonselective (complete) removal of all carious dentine; however, the promotion of minimally invasive biologically based treatment strategies has been advocated for selective (partial) caries removal and a reduced risk of pulp exposure. Selective caries removal strategies can be one‐visit as indirect pulp treatment or two‐visit using a stepwise approach. Management strategies for the treatment of the cariously exposed pulp are also shifting with avoidance of pulpectomy and the re‐emergence of vital pulp treatment (VPT) techniques such as partial and complete pulpotomy. These changes stem from an improved understanding of the pulp–dentine complex's defensive and reparative response to irritation, with harnessing the release of bioactive dentine matrix components and careful handling of the damaged tissue considered critical. Notably, the development of new pulp capping materials such as mineral trioxide aggregate, which although not an ideal material, has resulted in more predictable treatments from both a histological and a clinical perspective. Unfortunately, the changes in management are only supported by relatively weak evidence with case series, cohort studies and preliminary studies containing low patient numbers forming the bulk of the evidence. As a result, critical questions related to the superiority of one caries removal technique over another, the best pulp capping biomaterial or whether pulp exposure is a negative prognostic factor remain unanswered. There is an urgent need to promote minimally invasive treatment strategies in Operative Dentistry and Endodontology; however, the development of accurate diagnostic tools, evidence‐based management strategies and education in management of the exposed pulp are critical in the future.

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“…) can also contribute to reparative events (Okamoto et al . ). In addition, it is apparent that early inflammatory defence responses that resolve can lead to a promotion of regenerative events, whilst more concerted, prolonged and intense inflammation can lead to a shift in the balance of events away from regeneration (Cooper et al .…”

Section: Introductionmentioning

confidence: 97%

Dissecting dentine–pulp injury and wound healing responses: consequences for regenerative endodontics

2019

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Summary A thorough understanding of the biology of the dentine–pulp complex is essential to underpin new treatment approaches and maximize clinical impact for regenerative endodontics and minimally invasive vital pulp treatment (VPT) strategies. Following traumatic and carious injury to dentine–pulp, a complex interplay between infection, inflammation and the host defence responses will occur, which is critical to tissue outcomes. Diagnostic procedures aim to inform treatment planning; however, these remain clinically subjective and have considerable limitations. As a consequence, significant effort has focussed on identification of diagnostic biomarkers, although these are also problematic due to difficulties in identifying appropriate diagnostic fluid sources and selecting reproducible biomarkers. This is further compounded by the link between inflammation and repair as many of the molecules involved exhibit significant multifunctionality. The tertiary dentine formed in response to dental injury has been purposefully termed reactionary and reparative dentine to enable focus on associated biological processes. Whilst reactionary dentine produced in response to milder injury is generated from surviving primary odontoblasts, reparative dentine, in response to more intense injury, requires the differentiation of new odontoblast‐like cells derived from progenitor/stem cells recruited to the injury site. These two diverse processes result in very different outcomes in terms of the tertiary dentine produced and reflect the intensity rather than specific nature (nonexposure versus exposure) of the injury. The subsequent identification of the odontoblast‐like cell phenotype remains challenging due to lack of unique molecular or morphological markers. Furthermore, the cells ultimately lining the newly deposited dentine provide only a snapshot of events. The specific source and plasticity of the progenitor cells giving rise to the odontoblast‐like cell phenotype are also of significant debate. It is likely that improved characterization of tertiary dentine may better clarify the influence of cell derivation for odontoblast‐like cells and their diversity. The field of regenerative endodontics offers exciting new treatment opportunities, and to maximize outcomes, we propose that the term regenerative endodontics should embrace the repair, replacement and regeneration of dentine–pulp.

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Dentinogenic effects of extracted dentin matrix components digested with matrix metalloproteinases

Cited by 41 publications

References 73 publications

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

Management of deep caries and the exposed pulp

Dissecting dentine–pulp injury and wound healing responses: consequences for regenerative endodontics

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