Non-Cochrane · aetiology · PM38029242
Presence of host and bacterial-derived collagenolytic proteases in carious dentin: a systematic review of ex vivo studies.
Barbosa Cecília de Brito, Monici Silva Isabela, de Cena Jéssica Alves, et al. · Frontiers in cellular and infection microbiology · 2023 · PubMed · doi:10.3389/fcimb.2023.1278754
Full textEvery question was extracted from the full text, figures and supplements by two independent LLM extractors, disagreements adjudicated. Rows cite where in the review the value comes from.
Questions
38
current version
GRADE rated
30
No studies
0
Included studies
18
linked below
No studies 0 · 0%Ungraded 8 · 21.1%Very low 28 · 73.7%Low 0 · 0%Moderate 2 · 5.3%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Human dentin or biofilms with natural caries lesions (ex vivo extracted teeth or clinical carious/biofilm samples) | Human ex vivo carious dentin/biofilm (n=18 studies; 3-42 samples each, mean ~15) |
| Intervention | Carious dentin/lesion; host and bacterial-derived collagenolytic proteases (MMPs, cysteine cathepsins, bacterial collagenases) | Host collagenases MMP-2, MMP-8, MMP-9, MMP-13, MMP-20, cathepsins CT-B/CT-K (n=14 studies); bacterial collagenolytic proteases (n=4 studies) |
| Comparison | Sound dentin and paired comparators (root vs coronal; outer vs inner; before vs after sealing; irradiated vs non-irradiated) | Sound dentin; coronal vs root; outer vs inner; before vs after cavity sealing; irradiated vs non-irradiated; sound root/enamel caries (bacterial) |
| Outcomes | Presence/activity/expression of collagenolytic proteases; effect direction of statistically significant differences | Effect direction of protease presence/activity; GRADE certainty (mostly very low; MMP-20 outer vs inner moderate) |
| Study designs | Observational (cross-sectional, case-control, cohort) and experimental (randomized/non-randomized) ex vivo studies | Ex vivo observational studies (n=18; 14 host, 4 bacterial) |
| Timing | No time restriction | Not specified (Kuhn et al., 2016: 60 days post-sealing) |
Search date: March 2022. Databases: MEDLINE via PubMed; LILACS; Web of Science; Scopus; Cochrane; EMBASE; Livivo; grey literature: Google Scholar, ProQuest (Dissertations and Theses), OpenGrey (abstract states eight databases plus grey literature)
Questions and results
Carious dentin vs Sound dentin
Population: Human coronal carious dentin and sound dentin
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
MMP-13 presence/activity MMP-13 may be increased in carious dentin compared with sound dentin (very low certainty). Source: Results: Sound vs. carious; Table 2 · same question in other reviews | no estimate extracted | 1 study · 13 participants | Very low |
MMP-8 presence/activity Population: Human ex vivo carious dentin (mostly coronal), natural caries lesions For MMP-8, no clear direction of difference between carious and sound dentin was found; the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-8, GRADE evidence profile); Results (Sound vs. carious) · same question in other reviews | Due to the conflicting results of the included studies, no effect direction was found so the evidence is very uncertain regarding the MMP-8 presence in carious vs. sound dentin. | 2 studies | Very low Downgraded: risk of bias, imprecision, inconsistency |
MMP-2 presence/activity MMP-2 may be increased in carious dentin compared with sound dentin (very low certainty). Source: Results: Sound vs. carious; Table 2 · same question in other reviews | no estimate extracted | 7 studies · 373 participants | Very low Downgraded: risk of bias, imprecision |
MMP-9 presence/activity MMP-9 may be increased in carious dentin compared with sound dentin (very low certainty). Source: Results: Sound vs. carious; Table 2 · same question in other reviews | no estimate extracted | 3 studies | Very low Downgraded: inconsistency |
Cathepsin K (CT-K) presence/activity Population: Human ex vivo carious dentin (mostly coronal), natural caries lesions Cathepsin K may be increased in carious dentin (one study), but no certainty rating was assigned (ungraded). Source: Results (Sound vs. carious); Table 1 (Vidal et al., 2014) · same question in other reviews | Higher intensity of immunodetection of CT-K was registered in carious dentin than in sound dentin (Vidal et al., 2014); GRADE was not applied to CT-K. | 1 study · 10 participants | Ungraded |
MMP-13 presence/activity Population: Human ex vivo carious dentin (mostly coronal), natural caries lesions MMP-13 may be increased in carious dentin compared with sound dentin, but the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-13, GRADE evidence profile); Results (Sound vs. carious); Abstract · same question in other reviews | MMP-13 may be increased in carious dentin when compared to sound dentin, but the evidence is very uncertain (Loreto et al., 2014: more in coronal caries, p<0.05). | 1 study · 13 participants | Very low Downgraded: risk of bias, imprecision |
MMP-8 presence/activity No effect direction was found for MMP-8 in carious versus sound dentin (very low certainty). Source: Results: Sound vs. carious; Table 2 · same question in other reviews | no estimate extracted | 2 studies | Very low |
MMP-2 presence/activity Population: Human ex vivo carious dentin (mostly coronal), natural caries lesions MMP-2 may be increased in carious dentin compared with sound dentin, but the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-2, GRADE evidence profile); Results (Sound vs. carious); Abstract · same question in other reviews | MMP-2 may be increased in carious dentin when compared to sound dentin, but the evidence is very uncertain. | 7 studies · 373 participants | Very low Downgraded: risk of bias, imprecision |
MMP-9 presence/activity Population: Human ex vivo carious dentin (mostly coronal), natural caries lesions MMP-9 may be increased in carious dentin compared with sound dentin, but the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-9, GRADE evidence profile); Results (Sound vs. carious); Abstract · same question in other reviews | MMP-9 may be increased in carious dentin when compared to sound dentin, but the evidence is very uncertain. | 3 studies · 292 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Cathepsin B (CT-B) presence/activity Population: Human ex vivo carious dentin (mostly coronal), natural caries lesions Cathepsin B may be increased in carious dentin compared with sound dentin, but the evidence is very uncertain (very low certainty). Source: Table 2 (CT-B, GRADE evidence profile); Results (Sound vs. carious); Abstract · same question in other reviews | CT-B may be increased in carious dentin when compared to sound dentin, but the evidence is very uncertain (Vidal et al., 2014; Nascimento et al., 2011: significantly higher in caries, p<0.05). | 2 studies · 22 participants | Very low Downgraded: risk of bias, imprecision |
Cathepsin B presence/activity Cathepsin B may be increased in carious dentin compared with sound dentin (very low certainty). Source: Results: Sound vs. carious; Table 2 · same question in other reviews | no estimate extracted | 2 studies · 22 participants | Very low |
Root carious dentin vs Coronal carious dentin
Population: Human ex vivo carious dentin (coronal and root)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
MMP-2 presence/activity MMP-2 shows no difference between root and coronal carious dentin; the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-2); Results (Coronal vs root); Abstract · same question in other reviews | There is no difference in MMP-2 activity in root vs. coronal carious dentin; MMP-2 was present in both coronal and root dentin in all specimens (Toledano et al., 2010). The evidence is very uncertain. | 1 study · 10 participants | Very low Downgraded: risk of bias, imprecision |
MMP-2 activity Population: Human root and coronal carious dentin No difference in MMP-2 activity was found in root versus coronal carious dentin (very low certainty). Source: Results: Coronal vs. root dentin caries; Table 2 · same question in other reviews | no estimate extracted | 1 study · 10 participants | Very low |
MMP-13 presence/activity MMP-13 may be increased in root compared with coronal carious dentin, but the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-13); Results (Coronal vs root); Abstract · same question in other reviews | MMP-13 may be increased in root caries when compared to coronal, but the evidence is very uncertain; no MMP-13 activity observed in the crown region by western blot (Yeon Lee et al., 2013). | 1 study · 7 participants | Very low Downgraded: risk of bias, imprecision |
MMP-13 activity Population: Human root and coronal carious dentin MMP-13 may be increased in root compared with coronal carious dentin (very low certainty). Source: Results: Coronal vs. root dentin caries; Table 2 · same question in other reviews | no estimate extracted | 1 study · 7 participants | Very low |
Outer carious dentin (by lesion depth/location) vs Inner carious dentin
Population: Human ex vivo carious dentin
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
MMP-8 location/depth MMP-8 showed no statistical difference by lesion location; the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-8); Results (Lesion depth and location) · same question in other reviews | Mixed: Kuhn 2016 no statistical difference by location; Shimada 2009 higher MMP-8 in outer vs inner carious dentin (very low certainty) | 2 studies | Very low Downgraded: risk of bias, imprecision |
MMP-9 location/depth Population: Human carious dentin Opposite effect directions were reported for MMP-9 by lesion depth or location (very low certainty). Source: Results: Lesion depth and location; Table 2 · same question in other reviews | no estimate extracted | 3 studies | Very low Downgraded: inconsistency |
MMP-2 location/depth No clear direction of MMP-2 presence by lesion depth/location was found; the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-2); Results (Lesion depth and location) · same question in other reviews | The evidence is very uncertain about the MMP-2 location in dentin, as no effect direction was found (MMP-2 ubiquitous and variable across regions). | 4 studies | Very low Downgraded: risk of bias, imprecision, inconsistency |
MMP-2 location/presence Population: Human carious dentin No effect direction was found for MMP-2 by lesion depth or location (very low certainty). Source: Results: Lesion depth and location; Table 2 · same question in other reviews | no estimate extracted | 4 studies | Very low Downgraded: inconsistency |
MMP-20 location/depth (outer vs inner) MMP-20 probably decreases in outer compared with inner carious dentin (moderate certainty). Source: Table 2 (MMP-20); Results (Lesion depth and location); Discussion; Abstract · same question in other reviews | MMP-20 probably reduces in carious outer dentin when compared to carious inner dentin (moderate certainty); MMP-20 was significantly lower in outer dentin than inner (Shimada et al., 2009). | 1 study · 5 participants | Moderate |
MMP-8 location/presence Population: Human carious dentin Evidence on MMP-8 by lesion depth or location was very low certainty. Source: Results: Lesion depth and location; Table 2 · same question in other reviews | No clear single direction for MMP-8 by lesion depth/location (Kuhn 2016 NS by location; Shimada 2009 higher in outer); very low | 2 studies | Very low |
MMP-9 location/depth No clear direction of MMP-9 expression by lesion depth/location was found; the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-9); Results (Lesion depth and location) · same question in other reviews | The evidence is very uncertain about the MMP-9 expression in different locations and lesion depth, as studies showed opposite effect directions. | 3 studies | Very low Downgraded: risk of bias, imprecision, inconsistency |
MMP-20 expression Population: Human carious dentin MMP-20 probably reduces in outer compared with inner carious dentin (moderate certainty). Source: Results: Lesion depth and location; Table 2 · same question in other reviews | no estimate extracted | 1 study · 5 participants | Moderate |
Before cavity sealing vs After cavity sealing
Population: Human carious dentin
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
MMP-8 expression/activity 60 days after cavity sealing MMP-8 may be increased before compared with after cavity sealing (very low certainty). Source: Results: Before and after cavity sealing; Table 2 · same question in other reviews | no estimate extracted | 2 studies · 48 participants | Very low Downgraded: imprecision |
MMP-8 expression/activity Before vs after sealing (Kuhn 2016: 60 days follow-up) Population: Human ex vivo carious dentin under sealed cavities MMP-8 may be higher before than after cavity sealing, but the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-8); Results (Before and after cavity sealing); Abstract · same question in other reviews | MMP-8 may be increased in the dentin before when compared to dentin after cavity sealing; MMP-8 significantly reduced after 60 days of sealing (Kuhn et al., 2016; Chibinski et al., 2014). | 2 studies · 48 participants | Very low Downgraded: risk of bias, imprecision |
MMP-9 expression/activity 60 days after cavity sealing No difference in MMP-9 expression/activity was found before versus after cavity sealing (very low certainty). Source: Results: Before and after cavity sealing; Table 2 · same question in other reviews | no estimate extracted | 2 studies · 48 participants | Very low Downgraded: imprecision |
MMP-9 expression/activity Before vs after sealing (Kuhn 2016: 60 days follow-up) Population: Human ex vivo carious dentin under sealed cavities MMP-9 shows no difference before vs after cavity sealing; the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-9); Results (Before and after cavity sealing); Abstract · same question in other reviews | There is no difference of MMP-9 expression/activity before and after cavity sealing, although the evidence is very uncertain. | 2 studies · 48 participants | Very low Downgraded: risk of bias, imprecision |
MMP-2 expression/activity 60 days after cavity sealing No difference in MMP-2 expression/activity was found before versus after cavity sealing (very low certainty). Source: Results: Before and after cavity sealing; Table 2 · same question in other reviews | no estimate extracted | 2 studies · 48 participants | Very low Downgraded: imprecision |
MMP-2 expression/activity Before vs after sealing (Kuhn 2016: 60 days follow-up) Population: Human ex vivo carious dentin under sealed cavities MMP-2 shows no difference before vs after cavity sealing; the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-2); Results (Before and after cavity sealing); Abstract · same question in other reviews | There is no difference of MMP-2 expression/activity before and after cavity sealing, although the evidence is very uncertain. | 2 studies · 48 participants | Very low Downgraded: risk of bias, imprecision |
Irradiated carious dentin vs Non-irradiated carious dentin
Population: Human ex vivo carious dentin (head/neck radiotherapy)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
MMP-2 expression/activity MMP-2 showed no difference between irradiated and non-irradiated carious dentin (one study; ungraded). Source: Results (Irradiated vs non-irradiated); Table 1 (Gomes-Silva et al., 2017a) · same question in other reviews | No significant difference in MMP-2 (gelatinase) expression or activity between irradiated and non-irradiated groups (Gomes-Silva et al., 2017a); GRADE not separately applied to this comparison. | 1 study · 36 participants | Ungraded |
MMP-9 expression/activity MMP-9 showed no increase in irradiated vs non-irradiated carious dentin (one study; ungraded). Source: Results (Irradiated vs non-irradiated); Table 1 (Gomes-Silva et al., 2017a) · same question in other reviews | MMP-9 predominantly positive in non-irradiated vs irradiated carious dentin (single study; ungraded) | 1 study · 36 participants | Ungraded |
MMP-2 activity/expression Population: Human carious dentin from irradiated and non-irradiated subjects No difference in MMP-2 activity or expression was reported between irradiated and non-irradiated carious dentin. Source: Results: Irradiated vs. non-irradiated dentin · same question in other reviews | no estimate extracted | 1 study · 36 participants | Ungraded |
MMP-20 expression Population: Human carious dentin from irradiated and non-irradiated subjects No difference in MMP-20 expression was found between irradiated and non-irradiated carious dentin (very low certainty). Source: Results: Irradiated vs. non-irradiated dentin; Table 2 · same question in other reviews | no estimate extracted | 1 study · 36 participants | Very low |
MMP-20 expression/activity MMP-20 shows no difference between irradiated and non-irradiated carious dentin; the evidence is very uncertain (very low certainty). Source: Table 2 (MMP-20); Results (Irradiated vs non-irradiated); Abstract · same question in other reviews | There is no difference about the MMP-20 expression in irradiated vs. non-irradiated carious dentin, but the evidence is very uncertain (Gomes-Silva et al., 2017b). | 1 study · 36 participants | Very low Downgraded: risk of bias, imprecision |
Caries-associated bacterial biofilm vs Sound/control tissue (sound dentin, sound root, or enamel caries)
Population: Human ex vivo carious lesions / caries-associated biofilm
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Bacterial collagenolytic protease gene expression Genes encoding bacterial collagenolytic proteases were detected/overexpressed in coronal and root caries (ungraded; GRADE not feasible). Source: Table 3 (Collagenases gene expression); Results (Omics) · same question in other reviews | Genes coding for bacterial collagenolytic proteases were significantly expressed/overrepresented in coronal (Simon-Soro et al., 2013) and root (Dame-Teixeira et al., 2018: 42 proteases differentially expressed, 18… | 2 studies · 25 participants | Ungraded |
Bacterial collagenolytic enzymatic activity Bacterial collagenolytic enzymatic activity in caries biofilm is inconclusive across two small studies (ungraded; GRADE not feasible). Source: Table 3 (Collagenase activity); Results (Collagenase enzymatic assays) · same question in other reviews | Results are inconclusive: protein-degrading bacteria isolated from root caries biofilm were capable of degrading collagen (Prevotella, Actinobaculum, Propionibacterium predominant; proportion 7% in root caries)… | 2 studies · 9 participants | Ungraded |
Dentin caries vs Enamel caries
Population: Coronal dentin and enamel caries samples
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Bacterial collagenolytic-protease gene expression Genes encoding collagenases and other proteases were overrepresented in dentin caries compared with enamel caries. Source: Results: Omics; Table 3 · same question in other reviews | no estimate extracted | 1 study | Ungraded |
Root caries lesion biofilm vs Sound-site supragingival biofilm
Population: Root caries lesion biofilm
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Collagen-degrading bacteria Protein-degrading bacteria capable of degrading collagen were detected in root caries biofilm. Source: Results: Collagenase enzymatic assays; Table 3 · same question in other reviews | no estimate extracted | 1 study | Ungraded |
Included primary studies 18
Open as a trial list| Study | Also included by | Outcomes it informs here | Trial PICO | Results |
|---|---|---|---|---|
| Ballal et al. 2017 MMP-9 in Dentinal Fluid Correlates with Caries Lesion Depth. PMID:28848154 | this review only | not stated | not extracted yet | not extracted yet |
| Bello Arroyo 2016 matched by author and year (probable) | this review only | not stated | not extracted yet | not extracted yet |
| Boushell et al. 2011 Increased matrix metalloproteinase-2 and bone sialoprotein response to human coronal caries. PMID:21876355 | this review only | not stated | not extracted yet | not extracted yet |
| Charadram et al. 2012 Regulation of reactionary dentin formation by odontoblasts in response to polymicrobial invasion of dentin matrix. PMID:22079283 | this review only | not stated | not extracted yet | not extracted yet |
| Chibinski et al. 2014 Bone sialoprotein, matrix metalloproteinases and type I collagen expression after sealing infected caries dentin in primary teeth. PMID:24556583 | this review only | not stated | not extracted yet | not extracted yet |
| Dame-Teixeira et al. 2018 Gene expression of bacterial collagenolytic proteases in root caries. PMID:34394852 | this review only | not stated | not extracted yet | not extracted yet |
| Gomes-Silva et al. 2017a Head and neck radiotherapy does not increase gelatinase (metalloproteinase-2 and -9) expression or activity in teeth irradiated in vivo. PMID:28602264 | this review only | not stated | not extracted yet | not extracted yet |
| Gomes-Silva et al. 2017b Postradiation Matrix Metalloproteinase-20 Expression and Its Impact on Dental Micromorphology and Radiation-Related Caries. PMID:28359051 | this review only | not stated | not extracted yet | not extracted yet |
| Hashimoto et al. 2011 Profiling of dental plaque microflora on root caries lesions and the protein-denaturing activity of these bacteria. PMID:22165457 | this review only | not stated | not extracted yet | not extracted yet |
| Kuhn et al. 2016 Effect of sealing infected dentin with glass ionomer cement on the abundance and localization of MMP-2, MMP-8, and MMP-9 in young… PMID:25967636 | this review only | not stated | not extracted yet | not extracted yet |
| Loreto et al. 2014 Immunohistochemical analysis of matrix metalloproteinase-13 in human caries dentin. PMID:24704999 | this review only | not stated | not extracted yet | not extracted yet |
| Nascimento et al. 2011 Cysteine cathepsins in human carious dentin. PMID:21248362 | this review only | not stated | not extracted yet | not extracted yet |
| Shimada et al. 2009 Localization of matrix metalloproteinases (MMPs-2, 8, 9 and 20) in normal and carious dentine. PMID:20415934 | this review only | not stated | not extracted yet | not extracted yet |
| Simon-Soro et al. 2013 A tissue-dependent hypothesis of dental caries. PMID:24080530 | this review only | not stated | not extracted yet | not extracted yet |
| Tjaderhane et al. 1998 The activation and function of host matrix metalloproteinases in dentin matrix breakdown in caries lesions. PMID:9719036 | this review only | not stated | not extracted yet | not extracted yet |
| Toledano et al. 2010 Differential expression of matrix metalloproteinase-2 in human coronal and radicular sound and carious dentine. PMID:20452393 | this review only | not stated | not extracted yet | not extracted yet |
| Vidal et al. 2014 Abundance of MMPs and cysteine cathepsins in caries-affected dentin. PMID:24356440 | this review only | not stated | not extracted yet | not extracted yet |
| Yeon Lee et al. 2013 MMP-13 expression in coronal and radicular dentin according to caries progression -a pilot study DOI:10.1007/s13770-013-1095-8 | this review only | not stated | not extracted yet | not extracted yet |