Evidence Related to Study of Various Biomarkers and Proteins in Various Biofluids Associated to EARR.
Evidence Related to Study of Various Biomarkers and Proteins in Various Biofluids Associated to EARR.
| Authors | Experimental Subjects/Teeth (No./Age/Sex) | Biomarkers Studied | Condition Analyzed | Detection of Root Resorption | Controls/Teeth (No./Age/Sex) | Medium Studied | Technique | Outcomes | Conclusions |
|---|---|---|---|---|---|---|---|---|---|
| 2004 Mah et al.13 | Grp 1: Mx central incisor (n=20) with 1–3 mm RR; 13F, 7M; 12–16 y
Grp 2: 10 second molars (n=20); 15F, 5M; 9–12 y |
DPP | Orthodontic Tx (not specified) | Radiographs (not specified) | Mx central incisors (n=20) of untreated pts, 12F, 8M, 12–16 y | GCF | Periopaper, ELISA | Levels of DPP: greatest in resorbing 10 molar (11.7±4.1 μg/mg) followed by orthodontically treated tooth (9.3±4.7 μg/mg) and least in controls (5.4±4.1 μg/mg); NS between resorption Grps | DPP can be detected in exfoliating primary teeth and orthodontic root resorption |
| 2007 Balducci et al.7 | 20 pts with mild RR (≤2 mm) (11F, 9M, 14–40 y), 20 pts with severe RR (>2 mm) (15F, 5M, 15–44 y) | DMP1, PP, DSP | RR in orthodontic pts | IOPA | 20 pts (13F, 7M, 12–34 y); no RR/orthodontic Tx | GCF | Periopaper (mesial and distal of Mx central and lateral incisors), SDS–PAGE, stained western blot, ELISA | Molecular weight 77, 66, 55, 50, and 26 kDa proteins identified, NS between control and study Grps in immunoblot; ELISA showed Sig. ↑ of DMP1, PP, DSP in RR vs control Grps and of PP and DSP in severe RR vs mild RR Grps | DMP1, DSP, and PP in GCF proved a biomarker for RR in orthodontic Tx |
| 2008 Kereshanan et al.5 | Grp 1: 50 second 10 molars (9–14 y) (advanced coronal RR [n=33] and apical minimal RR Grp [n=17])
Grp 2: 20 pts (11–15 y), T0=pre-fixed Tx, T1=12 mo post start of Tx |
DSP | Physiological RR and OTM | Orthopantomogram | Control: 20 pts (10–15 y) erupted second premolars with no RR | GCF | Micropipettes, slot blot immunoassay, DSP in dentin of 10 molars by western blot | DSP levels: greater in physiological RR than non-resorbing teeth, DSP levels NS between coronal RR and apical RR; DSP levels Sig. higher in T1 compared to T0 | DSP in GCF proved a biomarker of root resorption |
| 2009 George et al.19 | Grp 1: mild RR of 2 mm (20 pts, Tx 1 y)
Grp 2: severe RR >2 mm (20 pts) |
OPN, OPG, RANKL | Orthodontic Tx (not specified) | Radiographs (not specified) | 20 pts: no Tx, no RR | GCF | Periopaper (mesial/distal of Mx central and lateral incisors), SDS-PAGE, western blot | Proteins conc greater in severe RR (0.89 μg/μL ±0.32 μg) than mild RR (0.77 μg/μL ±0.21 μg) and least in controls (0.22 μg/μL ±0.05 μg); ELISA showed Sig. higher RANKL antibodies in RR Grps than control Grp; RANKL/OPG ratio in severe RR Sig. greater than in control Grp | Presence of OPN, OPG, and RANKL in root resorption |
| 2013 Kunii et al.9 | 5 pts with severe RR (5F, mean age 28.9±6.1 y; mean orthodontic Tx duration of 27.8±3.3 mo) | IL-6 | All 4 extr orthodontic Tx | Radiographs (not specified) | 15 pts without RR (13F, 2M, mean age, 28.0±5.3 y; mean orthodontic Tx duration of 26.4±3.1 mo) | GCF | Periopaper (mesial/distal of Mx central and lateral incisors), ELISA | IL-6 protein levels Sig. ↑ in RR than non-RR Grp | IL-6 in GCF proved a root resorption biomarker in orthodontic Tx |
| 2013 Wahab et al.15 | 12F (Mx canines as test teeth), 100 g/150 g force to either side, split mouth design | ALP | Class II div 1 malocc; upper 4/4 extr with retraction by NiTi coil spring | IOPA | Mand canine as control | GCF, collection weekly for 6 wk | Periopaper (mesial/distal of Mx canine, Mand canine), spectrophotometry at 405 nm | ALP at mesial sites peak at wk 1 showing Sig. diff with 100 g force; no RR for test/control teeth in 150/100 g force | Canine movement greater with 150 g than 100 g force and higher ALP at mesial sites with no RR |
| 2014 Sha et al.2 | 20 pts (12F, 8M, 13–24 y), 8–12 mo of orthodontic Tx | DSPP | Orthodontic Tx (not specified) | Radiographs (not specified) | Same pts for both methods (ELISA with spectrophotometry and electrochemical detection) | GCF | Filter paper strip (mesial/distal sites of left and right Mx central incisors), ELISA | DSPP detection with spectrophotometric ELISA 10 times greater than with electrochemical detection. DSPP conc range NS between methods | DSPP can be sensitively and accurately detected in root resorption |
| 2014 Vieira20 | Total 60 pts (38F, 22M, 15–30 y with orthodontic Tx of 6 mo); Grp 2: 30 pts, mild to moderate RR | Proteins | Orthodontic Tx (not specified) | IOPA | Grp 1: 30 pts, no RR | GCF | Sterile absorbent paper cones, 2-DE gels, SDS-PAGE with isoelectric focusing | Greatest sharpness to detect protein bands with Milli-Q ultrapure ice-cold water, without GCF protein extraction | Protein extraction protocols tested for accuracy |
| 2014 Rody et al.21 | 11 pts (7F, 4M, 10–11 y) second 10 molars with RR in one quadrant; split mouth design | Proteins | No orthodontic Tx | Radiograph (not specified) | 11 pts (7F, 4M, 10–11 y), permanent 1st molar on contralateral side with no RR | GCF | Periopaper (lingual side of 10 and permanent molars), LC-MS, nano-flow LC system coupled to triple TOF 5600 MS | Total 37 RR proteins upregulated and 59 RR proteins downregulated | RR proteins upregulation and downregulation identified in RR |
| 2015 Wahab et al.22 | 19 (13F, 6M), split mouth design, either 100 g or 150 g force | ALP, TRAP, AST | All 4 extr and retr | IOPA | Internal control (baseline) | GCF, Baseline (0 wk), 1–5 wk | Periopaper (mesial/distal of Mx right and left canine), spectrophotometry | 100 g Grp: TRAP Sig. ↑ from baseline to 3–5 wk and slight rise of ALP, AST from baseline; 150 g Grp: ALP, TRAP activities ↑ slightly from baseline, AST Sig. ↑ in 5 wk | 150 g force and 100 g force show NS difference in AST, ALP, or TRAP levels |
| 2016 Lombardo et al.23 | 6 pts (5F, 1M), average age 14 y, 12 wks orthodontic Tx | DSP | Orthodontic treatment with Damon appliances | Radiographs (not specified) | Same pts for both methods (conventional ELISA vs DSP antibody-coated magnetic micro-beads prior to ELISA) | GCF | Mesial and Ds sites of Mx central and lateral incisors, sterile paper strips | Sig. diff between standard ELISA and micro-beads for DSP evaluation in early RR evaluation; results of micro-bead approach are more uniform and highly sensitive | Modified micro-bead approach is more reliable for early detection of RR for DSP evaluation |
| 2016 Rody et al.16 | 11 pts (7F, 4M, 10–11 y), second 10 molars with RR in one quadrant | IL-1β, IL-1RA, MMP-8, DSP, RANKL, OPG | No orthodontic Tx | Radiograph (not specified) | Permanent 1st molar on contralateral side with no RR | GCF | Lingual side of 10 and permanent molars, Periopaper, immunoassay | NS in IL-1β, OPG, or MMP-9 between exp and control Grp; RANKL data unreliable; IL-1RA Sig. downregulated in RR | IL-1RA down-regulation in GCF from 10 molars with root resorption |
| 2017 Yashin et al.12 | 9 pts (mean age 23±2.9 y), moderate to severe RR | Cytokine profile in saliva | Finished orthodontic Tx within 2 y | Orthopantomograms | Pts with no RR | Blood and saliva | 10 mL unstimulated saliva collected by expectoration, ELISA | Saliva: moderate to severe RR show Sig. ↑ in IL-7, IL-10, IL-12p70, and IFN-γ, Sig. ↓ in IL-4; blood: control group has higher osteocalcin and P1NP than RR | Saliva can be used for cytokine assessment in root resorption |
| 2017 Kaczor-Urbanowicz et al.24 | 48 pts with RR (31F, 17M)
Grp 1: moderate to severe RR young pts (11F, 6M); Grp 2: moderate to severe RR adult pts (7F, 4M); Grp 3: mild RR young pts (7F, 4M); Grp 4: mild RR adult pts (6F, 3M) |
Proteins | Not specified | IOPA (Mx central and lateral incisors) at T0 (before bonding), T9 (9 mo after bonding) | 24 pts without RR (13F, 11M)
Grp 5: control young pts (7F, 6M); Grp 6: control adult pts (6F, 5M) |
Saliva | Unstimulated whole saliva, 2D gel electrophoresis, quantitative mass spectrometry, western blot | 772 proteins identified by qMS, 244 highly increased expression profile, Sig. ↑ in moderate to severe young RR Grp compared to controls and 58 proteins in the adult Grp | Salivary proteins associated with root resorption identified |
| 2017 Thalanany et al.25 | 20 pts, 13–22 y; exp Grp: 10 pts undergoing orthodontic Tx | DSPP | Simultaneous intrusion and retr arch | Radiograph (not specified) | Control Grp: no orthodontic Tx | GCF, T0= before intrusion, T1=2 mo after intrusion | Mx right and left central and lateral incisors; microcapillary tubes, ELISA | Sig. ↑ in DSPP at T1 compared to T0 | DSPP may be marker for root resorption |
| 2017 Ahuja et al.26 | 8 (2F, 6M, age range 13.9–22.9 y)
Split mouth design: test vs control sides |
IL-1β, 2, 4, 5, 6, 7, 8, 10, 12, 13, INF-γ, TNF-α, GM-CSF | 225 g buccal tipping force for 28 d on test side | Micro-CT | Contralateral teeth (control side) | GCF, Time points: 0 h (prior to force), 3 h, 1 d, 3 d, 7 d, 28 d | Periopaper, multiplex bead immunoassay | IL-1β: Sig. ↑ peak at days 1 and 7 but NS between test and control side; IL-4: ↑, peak days 1–3; IFN-γ: peak at 72 h; TNF-α: ↑ at 3 h, 28 d; IL-7 peak at 28 d; GM-CSF: immediate ↓, ↑ at 7 d, peak at 28 d; Comparison between low and high RR: GM-CSF show Sig. ↑ in low RR; Micro-CT: mesial, distal surface, and middle 3rd showed sig. ↑ RR on test side teeth | Pro-resorptive cytokines (IL-7, TNF-α) ↑ in high orthodontic forces, anti- resorptive cytokines (GM-CSF) ↓ initially |
| 2018 Zhou et al.27 | 8F pts with RR, mean age 22.25 y, Tx duration 22.37 mo | Metabolites | Both extr and non-extr Tx | Orthopantomograms | 11F controls, mean age 24.27 y, Tx duration 21 mo | Saliva | Unstimulated saliva collected from occlusal space of right Mand molars without chewing for ~3 min | 187 metabolites identified, including butyrate, propane-1,2-diol, α-linolenic acid (Ala), α-glucose, urea, fumarate, formate, guanosine, and purine | Difference in metabolites in saliva of RR pts can be detected by 1 HNMR-based metabolomics method |
| 2020 Mohd Nasri et al.28 | 10 pts | Protein abundance | Mx and Mand fixed appliances | IOPA at T0 and T6 of Mx central incisors | None | GCF at T0 (pre-Tx), T1 (1 mo), T3 (3 mo), T6 (6 mo) | Mesial and Ds of Mx central incisors Periopaper, liquid chromatography-tandem mass spectrometry | Increased protein abundance of S100A9, immunoglobulin J chain; heat shock protein 1A, immunoglobulin heavy variable 4–34 and vitronectin at T1; protein abundance ↑ of thymidine phosphorylase at T3 | Early RR protein markers identified |
| 2021 Mandour et al.29 | 74 pts (3 Grps: 2 Tx, 1 control)
Grp 1: orthodontic pts (1–3 mm RR); Grp 2: pediatric pts (lower second 10 molars, physiologic RR) |
IL-1RA, DSPP | Not specified | Radiograph (not specified) | Grp 3: control (no RR, no orthodontic Tx) | GCF | Endodontic paper points, ELISA | IL-1RA levels in controls greater than orthodontic pts, and least in pediatric Grp; DSPP levels in pediatric group higher than in orthodontic pts, and least in controls; IL-1RA cut-off for OIRR (≤432.6 pg/mL) and DSPP (≥7.33 pg/mL); DSPP reliability (100%) vs IL-1RA (80%) | IL-1RA, DSPP biomarkers for OIRR |
| 2020 Zain et al.30 | 7 orthodontic pts, 2 samples taken at 3 and 6 mo into orthodontic Tx and 3 samples at 12 mo of orthodontic Tx | DSPP | Fixed orthodontic Tx | Not specified | 3 non-orthodontic control samples | GCF | Mx central incisors, Periopaper, absorption spectroscopy | Control sample showed lower peak in absorption spectrum than exp sample (3, 6, 12 mo); spectrum proportional to Tx duration, 0.91 accuracy | Higher absorption spectrum of DSPP indicates higher resorption |
↑, greater/increase; ↓, lower/decrease; 1 HNMR, hydrogen-1 nuclear magnetic resonance; 10, primary; ALP, alkaline phosphatase; AST, aspartate aminotransferase; conc, concentration; CT, computed tomography; d, day(s); diff, difference; DMP1, dentin matrix protein 1; DPP, dentin phosphophoryn; Ds, distal; DSP, dentin sialoprotein; DSPP, dentin sialophosphoprotein; EARR, external apical root resorption; ELISA, enzyme-linked Immunosorbent assay; exp, experimental; extr, extractions; F, female(s); GCF, gingival crevicular fluid; GM-CSF, granulocyte-macrophage colony-stimulating factor; Grp, group(s); h, hour(s); IFN-γ, interferon gamma; IL, interleukin; IL-RA, interleukin-1 receptor antagonist; IOPA, intraoral periapical radiograph; LC, liquid chromatography; LC-MS, liquid chromatography-mass spectrometry; M, male(s); malocc, malocclusion; Mand, mandibular; min, minute(s); MMP, matrix metalloproteinase; mo, month(s); MS, mass spectrometry; Mx, maxillary; NS, no statistically significant difference; OIRR, orthodontically induced root resorption; OPG, osteoprotegerin; OPN, osteopontin; OTM, orthodontic tooth movement; P1NP, procollagen type 1 N-terminal propeptide; PP, dentin phosphophoryn (alternate abbreviation in the literature); pts, patients; qMS, quadrupole mass analyzer; RANKL, receptor activator of nuclear kappa B ligand; retr, retraction; RR, root resorption; SDS-PAGE, Sodium dodecyl-sulfate polyacrylamide gel electrophoresis; Sig., significant; TNF-α, tumor necrosis factor-α; TOF, time of flight; TRAP, tartrate-resistant acid phosphatase; Tx, treatment; vs, versus; wk, week(s); y, year(s).