Periodontal Ligament Remodeling Research Articles

The Role of Periodontal Ligament Remodeling on Orthodontic Tooth Movement

The periodontal ligament is a connective tissue located between the cementum that covers the roots of the tooth and alveolar bone, which is composed of large amounts of fibers, cells, and blood vessels. Orthodontic tooth movements are obtained through periodontal ligament remodeling and alveolar bone in response to orthodontic forces. When the orthodontic force is applied to the teeth, an injury will occur in the periodontal ligament, and the pressure and tension side in the periodontal ligament is formed. Furthermore, vasoconstriction occurs in blood vessels and hypoxia in the periodontal ligament, triggering inflammation, angiogenesis, cell proliferation, degradation, and synthesis of extracellular matrix, bone resorption, and alveolar bone deposition. The purpose of this article is to study the mechanism of periodontal ligament remodeling on orthodontic tooth movement to obtain optimal tooth movements.

Periodontal ligament and alveolar bone remodeling during long orthodontic tooth movement analyzed by a novel user-independent 3D-methodology

The structural process of bone and periodontal ligament (PDL) remodeling during long-term orthodontic tooth movement (OTM) has not been satisfactorily described yet. Although the mechanism of bone changes in the directly affected alveolar bone has been deeply investigated, detailed knowledge about specific mechanism of PDL remodeling and its interaction with alveolar bone during OTM is missing. This work aims to provide an accurate and user-independent analysis of the alveolar bone and PDL remodeling following a prolonged OTM treatment in mice. Orthodontic forces were applied using a Ni–Ti coil-spring in a split-mouth mice model. After 5 weeks both sides of maxillae were scanned by high-resolution micro-CT. Following a precise tooth movement estimation, an extensive 3D analysis of the alveolar bone adjacent to the first molar were performed to estimate the morphological and compositional parameters. Additionally, changes of PDL were characterized by using a novel 3D model approach. Bone loss and thinning, higher connectivity as well as lower bone mineral density were found in both studied regions. Also, a non-uniformly widened PDL with increased thickness was observed. The extended and novel methodology in this study provides a comprehensive insight about the alveolar bone and PDL remodeling process after a long-duration OTM.

Mechanochemical coupling of MGF mediates periodontal regeneration.

Clinical evidence shows that the mechanical stimulation obtained from occlusion could enhance periodontal ligament (PDL) remodeling. Mechano-growth factor (MGF) is a growth factor produced specifically following mechanical stimulus Here, we aim to investigate the mechanical enhancement potential and mechanism of the MGF in PDL regeneration. In vivo study found that MGF produced from the PDL under occlusion force could strongly enhance PDL remodeling. In vitro experiments and mathematical modeling further confirmed the mechanical enhancement effect of MGF for PDLSC differentiation toward fibroblasts. A mechanochemical coupling effect of MGF mediated the enhancement of mechanical effect, which was modulated by Fyn-FAK kinases signaling and subsequent MAPK pathway. Finally, enhanced PDL regeneration under the mechanochemical coupling of MGF and occlusal force was verified in vivo. There exists an additive mechanical effect of MGF mediated by Fyn-FAK crosstalk and subsequent ERK1/2 and p38 phosphorylation, which could be developed as an MGF-centered adjuvant treatment to optimize PDL remodeling, especially for patients with weakened bite force or destroyed periodontium.

Ekspresi BMP2 dan TRAF6 pada Jaringan Periodontal setelah Pemberian Ekstrak Kopi Robusta selama Pergerakan Gigi Ortodonti

Orthodontic tooth movement occurs due to mechanical stimulation followed by alveolar bone and periodontal ligament remodeling. Bone remodeling is the process of bone resorption in areas of tension and bone formation in areas of tension. Various techniques and drugs are used to speed up orthodontic treatment. This study aims to analyze the expression of BMP2 and TRAP6 on orthodontic tooth movement after the administration of Robusta coffee extract. Twenty-four Wistar rats were divided into 4 groups: C1 (2 weeks) and C2 (3 weeks) groups: rats were given orthodontic mechanical force (OMF) and T1 (2 weeks) and T2 (3 weeks) groups rats were given OMF and Robusta coffee extract. OMF in rats was performed by moving the maxillary right permanent molars mesially with a Niti closed coil spring. Observations were made on the 15th and 22nd day by immunohistochemical examination to determine the expression of BMP2 and TRAP6. Administration of Robusta coffee extract for 2 weeks and 3 weeks increased BMP2 and TRAP6 expression (p <0.05). Administration of Robusta coffee extract increased the expression of BMP2 and TRAP6 in the alveolar bone during orthodontic tooth movement.

R-Spondins and Wnt Signalling Pathway: A Periodontal Perspective

Periodontitis is a multifactorial chronic condition associated with the formation of a dysbiotic biofilm, leading to inflammation that can modulate cell signaling. R-spondins (Rspos) are cysteine-rich secreted glycoproteins which control a variety of functions which are essential for embryonic development and tissue homeostasis. Numerous studies have explained about their pivotal role in critical developmental regulators, the most important finding being Rspos synergise Wingless/Integration (Wnt) signaling. Novel receptors for Rspos, the Leucine-rich repeat containing G protein-coupled (LGR) receptors, proposed that Rspos potentiate canonical Wnt signaling via these receptors. Here, authors discussed about the Wnt signaling and outlined the biological role of Rspos in tissue development and homeostasis and explore the possibility that Rspos may be used as therapeutic targets. Wnt5a is important for promoting periodontal ligament remodeling and impairing regenerative responses modulated by the Wnt/β-catenin pathway, for alveolar bone formation.

Wnt Signaling in Periodontal Disease

Periodontitis is a multifactorial and chronic condition associated with the formation of a dysbiotic biofilm, leading to a pro-inflammatory environment that can modulate cell signaling. The Wnt pathway plays fundamental roles during homeostasis and disease, and emerging evidence suggests its involvement in the maintenance of the periodontium and the development of periodontitis. Here, we summarize the role of the Wnt/β-catenin and non-canonical Wnt signaling pathways in periodontitis. The accumulated data suggests specific roles for each branch of the Wnt pathway. Wnt5a emerges as a critical player promoting periodontal ligament remodeling and impairing regenerative responses modulated by the Wnt/β-catenin pathway, such as alveolar bone formation. Collectively, the evidence suggests that achieving a proper balance between the Wnt/β-catenin and non-canonical pathways, rather than their independent modulation, might contribute to controlling the progression and severity of the periodontal disease.

The effect of hyperbaric oxygen 2.4 absolute atmospheres on transforming growth factor-β and matrix metalloproteinase-8 expression during orthodontic tooth movement in vivo

Context: Orthodontic force causes the compression of the periodontal ligament in inhibiting vascularization on the pressure side of orthodontic tooth movement (OTM), while on the opposite side, the periodontal ligament is stretched. Hyperbaric oxygen therapy (HBOT) can increase the dissolved oxygen in the blood, which can affect the tissue regeneration of the periodontal ligament. Aims: To evaluate the effect of HBO 2.4 absolute atmospheres (ATA) for 3 × 30 minutes with 5 minutes interval for 7 days as an adjuvant therapy to accelerate periodontal ligament remodeling during OTM in Cavia cobaya. Methods: The study was an experimental laboratory research with a completely randomized design. Twenty-four males C. cobaya were divided into three groups, (X1) as the control group, (X2) as the group with orthodontic force, and (X3) as the group with orthodontic force followed by HBO 2.4 ATA. Matrix Metalloproteinase (MMP)-8 and Transforming Growth Factor (TGF)-β expressions were measured by using immunohistochemistry. OTM was then examined by applying linear distance and analyzed by employing ratio test (p<0.05). Results: Ratio analysis shows HBO 2.4 ATA for 3 × 30 minutes once a day with 5 minutes intervals for 7 days has increased MMP-8 expressions in the pressure area and TGF-β in the tension area (p<0.05). Conclusions: HBO 2.4 ATA for 3 × 30 minutes once a day for 7 with 5 minutes intervals is able to effectively accelerate the periodontal ligament remodeling process expressed by the increased expression MMP-8, especially within the pressure area and TGF-β in the tension area.

Pyrophosphate inhibits periodontal ligament stem cell differentiation and mineralization through MAPK signaling pathways.

Periodontal ligament stem cells (PDLSCs) are the primary cell source for the regeneration and remodeling of periodontal ligament (PDL). It is crucial to prevent PDLSCs from mineralization when using the PDLSCs for PDL regeneration. At present, little is known about how to inhibit PDLSC mineralization. This study investigates the effects of pyrophosphate (PPi) on inhibiting PDLSC osteogenic differentiation and mineralization as well as the underlying mechanism. Human PDLSCs were cultured in an osteogenic differentiation medium with different PPi concentrations (0, 10, or 100μM). The effects of PPi on osteogenic differentiation were assessed by ALP activity and the expressions of osteogenic related proteins (OPN, RUNX2, OSX, and DMP1). The mineralization formation was detected by alizarin red staining. The activation of MAPK signaling pathways (ERK1/2, JNK, and p38) was determined by western blotting and pathway blockade assays. The gene expressions of PPi's regulators (Ank, Enpp1, and Alpl) were assessed by real-time PCR. Both low and high concentrations (10μM and 100μM) of PPi inhibited the mineralization of PDLSCs. The addition of PPi (10μM or 100μM) decreased the ALP activity of the PDLSCs to approximately two-thirds of the control group on day 3. PPi reduced the expressions of RUNX2, OSX, and DMP1 on days 7, 14, and 21, while it increased the expression of OPN at the three time points. PPi enhanced the phosphorylation of MAPK pathways, and the application of corresponding MAPK pathway inhibitors reversed the osteogenic inhibition effects of PPi. PPi inhibits the osteogenic differentiation and mineralization of PDLSCs in vitro through activating ERK1/2, JNK, and p38signaling pathways.

The Effect of Stichopus hermanii to TLR-4 in Mediating Periodontal Ligament Remodeling During Orthodontic Relapse

Stichopus hermanii contains an active compound that plays apart in the innate immune system. This research was aimed to investigate the effect of S. hermanii on the TLR-4 in mediating periodontal ligament (PDL) remodeling through fibroblast growth factor (FGF-2) and collagen type 1 parameter during orthodontic relapse. The true experimental using a post-test for the control group. Thirty-two male Guinea pig were distributed into four groups: K(−) group was the negative control group, K(+) group was the positive control group applied with orthodontic relapse forces, P1 group was applied with orthodontic relapse forces and 3% S. hermanii 3%, and the P2 group was applied with 3.5%. TLR-4, FGF-2, and collagen type-1 expression at the tension site was examined using immunohistochemistry. Analysis of Variance and Least Significance Difference tests were conducted for all specimens. TLR-4 in P1 and P2 were decreasing significantly (p≤0.05), while FGF-2 and collagen type 1 expression in P1 and P2 increased significantly (p≤0.05). Multiple regression test to correlate between parameters was also significant at 0.00 (p≤0.05). This study concluded that decrease of TLR-4 expression during orthodontic relapse showed a strong tendency to coincide with PDL remodeling along with increasing FGF-2 and collagen type 1 parameter. The optimum result in decreasing TLR-4 expression occurs when administered with S. hermanii 3.5%, which induces decreasing relapse to 29% and increasing periodontal remodeling, demonstrated by FGF-2 and collagen type-1 expression.

DR3 and its ligands take roles in periodontium remodeling during orthodontic tooth movement

Background/purposeBased on ‘pressure-tension theory’, the application of orthodontic force to the tooth site affects the remodeling of periodontal tissue, specifically, mechanical stress induces the release of cytokines. The purpose of this research paper is to examine death receptor 3/TNF-like protein 1A/progranulin (DR3/TL1A/PGRN) expression levels in periodontium tissue during orthodontic tooth movement in rats. Materials and methodsThirty-six ten-week-old male SD rats were used in this study. A total of 20 cN of orthodontic force was exerted by coil springs onto the upper right first molars in order for mesialization purposes. All rat members of their corresponding groups were euthanized based on the following time intervals: 0 day for the control group, 1 day (group two), 3 days (group three), 5 days (group four), 7 days (group five), and lastly 14 days for group six. The effects of DR3/TL1A/PGRN were observed through the use of immunohistochemical staining techniques. One-way analysis of variance followed by a LSD t-test was performed by SPSS 20 to compare the differences of the level of DR3/TL1A/PGRN amongst each specified time interval. ResultsThe expression levels of DR3/PGRN increased significantly on day 14 compared to that of the control group, thus indicating a wide range of statistical differences. The expression levels of TL1A soared upwards on day 1, then plunged to an all-time low on day 7 before finally bouncing back to its initial value on day14. ConclusionDR3 and its two ligands—PGRN and TL1A play indispensable roles in regulating periodontal ligament remodeling during orthodontic tooth movement.

Stress Distribution and Collagen Remodeling of Periodontal Ligament During Orthodontic Tooth Movement.

Periodontal ligament (PDL), as a mechanical connection between the alveolar bone and tooth, plays a pivotal role in force-induced orthodontic tooth movement (OTM). However, how mechanical force controls remodeling of PDL collagenous extracellular matrix (ECM) is largely unknown. Here, we aimed to evaluate the stress distribution and ECM fiber remodeling of PDL during the process of OTM. An experimental tooth movement model was built by ligating a coil spring between the left maxillary first molar and the central incisors. After activating the coil spring for 7 days, the distance of tooth movement was 0.324 ± 0.021 mm. The 3D finite element modeling showed that the PDL stress obviously concentrated at cervical margin of five roots and apical area of the mesial root, and the compression region was distributed at whole apical root and cervical margin of the medial side (normal stress < −0.05 MPa). After force induction, the ECM fibers were disordered and immature collagen III fibers significantly increased, especially in the apical region, which corresponds to the stress concentration and compression area. Furthermore, the osteoclasts and interleukin-1β expression were dramatically increased in the apical region of the force group. Taken together, orthodontic loading could change the stress distribution of PDL and induce a disordered arrangement and remodeling of ECM fibers. These findings provide orthodontists both mechanical and biological evidences that root resorption is prone to occur in the apical area during the process of OTM.

PENGARUH KOMBINASI TERAPI OKSIGEN HIPERBARIK DAN PROPOLIS TERHADAP DIAMETER PEMBULUH DARAH DI DAERAH TARIKAN LIGAMEN PERIODONTAL SELAMA PERGERAKAN GIGI UNTUK MENCEGAH RELAPS

&lt;strong&gt;&lt;em&gt;Background&lt;/em&gt;&lt;/strong&gt;&lt;em&gt;: The mechanical force of orthodontic device causes occurrence of a tension and a pressure area in the periodontal ligament. In the tension area, an inflammatory response characterized by vasodilation of blood vessels will occur. The function of blood vessel is to flow blood and other nutrients to accelerate the periodontal ligament remodeling process, so that relapse can be prevented. &lt;strong&gt;Objective:&lt;/strong&gt; To determine the effect of combination of propolis 3%, 5% for 14 days and HBOT 2,4 ATA 3x30 minutes with 5 minutes interval for 7 days in the tension area of the periodontal ligament as an effort to prevent relapse. &lt;strong&gt;Materials and Methods&lt;/strong&gt;: A randomized post-test only control group design was used in this study. 42 male guinea pigs (cavia cobaya) are divided into 7 groups K- (without treatment), K + (using separator), P1 (using separator and propolis extract 3%), P2 (using separator and propolis extract 5%), P3 (using separator and hyperbaric oxygen therapy), P4 (using separator and combination of hyperbaric oxygen therapy and 3% propolis extract), and P5 (using separator and combination of hyperbaric oxygen therapy and 5% propolis extract) . &lt;strong&gt;Results&lt;/strong&gt;: Data shows that mean of diameter of blood vessels increased from the smallest K- (41,8417±0,84511), K+(61,77±1,254482), P1(72,5983±0,68869), P2(73,2333±1,24481), P3(74,2583± 0,62030), P4(91,47±0,76585), to the largest in P5(91,5483±0,96178). One-way Anova and LSD test showed significant differences in blood vessels diameter (p &amp;lt;0.05). &lt;strong&gt;Conclusion&lt;/strong&gt;: The combination of propolis 3% and 5% and HBOT have significant effect in increasing blood vessels diameter in the tension area of the periodontal ligament&lt;/em&gt;

Periostin is essential for periodontal ligament remodeling during orthodontic treatment.

Orthodontic tooth movement is a process stimulated and maintained by external tensile stress; periodontal ligament remodeling serves an important role during this process. However, the function and underlying mechanism of periostin (PN) during orthodontic periodontal ligament remodeling remain unclear. The present study established invitro and invivo models of orthodontic treatment to investigate the expression levels of PN under conditions of external tensile stress load. These results indicated that tensile stress load increased the expression levels of PN in mouse peridontal ligaments and human periodontal ligament cells (hPDLCs), during orthodontic tooth movement. Furthermore, the present study demonstrated that the expression levels of PN were regulated by transforming grown factor β, and that PN promotes typeI collagen and α‑smooth muscle actin expression levels in hPDLCs. Therefore, PN may be essential for periodontal ligament remodeling during orthodontic treatment, and therefore may represent a potential therapeutic target.

FGF-2, MMP-8 and Integrin α2β1 Expression in Periodontal ligament Remodelling Tension Area with Nanopowder &amp;lt;i&amp;gt;Stichopus hermanii&amp;lt;/i&amp;gt; Application to Prevent Orthodontic Relapsing

Background: Orthodontic relapse tendency occurs 33–90 per cent after at least 10 years post-treatment. Orthodontic Relapsing is the return, following orthodontic correction, at the end of treatment. Relapse, a return to the original teeth position, caused by periodontal, occlusal, soft tissue factor and growth. Nanopowder Stichopus hermanii have various active ingredient such as protein, collagen, flavonoid, chondroitin sulphate, cell growth factor, EPA DHA, that might have role to FGF-2, MMP-8, Integrin α2β1 in periodontal ligament remodelling tension area in reducing orthodontic relapsing. Objectives: The aim of this study is to investigate application of Nanopowder Stichopus hermanii to prevent relaps orthodontic by periodontal ligament remodelling tension area through FGF-2, MMP-8, and Integrin α2β1 parameter. Material and Method: The experiment was held by Post Test Only Group design. Twenty four male Cavia Cobaya were divided into three groups. K(-) group as negative control group (without treatment), K(+) group as positive control group which were applied with relaps orthodontic forces, and the other groups P, were applied with relaps orthodontic forces and nanopowder Stichopus hermanii 3%. After treatment the cavia cobaya were sacrificed. FGF-2, MMP-8, and Integrin α2β1 expression is examined with immunohistochemistry. Results: Application nanopowder Stichopus hermanii can reduce relaps until 30%. This study showed FGF-2 expresssion are 13,9±2,6; 6,5±1,4; 21±4,6; MMP-8 expression means and SD in K(-), K(+), P are 3.75±1.49; 14.88±2.64; 9.13±1 and Integrin α2β1 expression are 5.25±1.28; 12.88±1.36; 16.50±2.33. There was significantly differences in group P compare to K(-) and K(+). Conclusion: Application of Nanopowder Stichopus hermanii have role in periodontal ligament remodeling tension area through increasing FGF-2, decreasing MMP-8, increasing Integrin α2β1 and Collagen type 1 parameter to prevent relaps orthodontic until 30%.

Residents' journal review

Residents' journal review

PDL Progenitor–Mediated PDL Recovery Contributes to Orthodontic Relapse

Periodontal ligament (PDL) is subjected to mechanical force during physiologic activities. PDL stem/progenitor cells are the main mesenchymal stem cells in PDL. However, how PDL progenitors participate in PDL homeostasis upon and after mechanical force is largely unknown. In this study, force-triggered orthodontic tooth movement and the following relapse were used as models to demonstrate the response of PDL progenitors and their role in PDL remodeling upon and after mechanical force. Upon orthodontic force, PDL collagen on the compression side significantly degraded, showing a broken and disorganized pattern. After force withdrawal, the degraded PDL collagen recovered during the early stage of relapse. Correspondingly, increased CD90+ PDL progenitors with suppressed expression of type I collagen (Col-I) were observed upon orthodontic force, whereas these cells accumulated at the degradation regions and regained Col-I expression after force withdrawal during early relapse. Our results further showed that compressive force altered cell morphology and repressed collagen expression in cultured PDL progenitors, which both recovered after force withdrawal. Force withdrawal–induced recovery of collagen expression in cultured PDL progenitors could be regulated by transforming growth factor–β (TGF-β), a key molecule for tissue homeostasis and extracellular matrix remodeling. More interesting, inhibiting the regained Col-I expression in CD90+ PDL progenitors by blocking TGF-β interrupted PDL collagen recovery and partially inhibited the early relapse. These data suggest that PDL progenitors can respond to mechanical force and may process intrinsic stability to recover to original status after force withdrawal. PDL progenitors with intrinsic stability are required for PDL recovery and consequently contribute to early orthodontic relapse, which can be regulated by TGF-β signaling.

Functional Role of HSP47 in the Periodontal Ligament Subjected to Occlusal Overload in Mice.

We carried out an experiment to induce traumatic occlusion in mice periodontal tissue and analyzed the expression of HSP47. Continuous traumatic occlusion resulted to damage and remodeling of periodontal ligament as well as increase in osteoclasts and bone resorption. Four days after traumatic occlusion, osteoclasts did not increase but Howship's lacunae became enlarged. That is, the persistent occlusal overload can destroy collagen fibers in the periodontal ligament. This was evident by the increased in HSP47 expression with the occlusal overload. HSP47 is maintained in fibroblasts for repair of damaged collagen fibers. On the other hand, osteoclasts continue to increase although the load was released. The osteoclasts that appeared on the alveolar bone surface were likely due to sustained activity. The increase in osteoclasts was estimated to occur after load application at day 4. HSP47 continued to increase until day 6 in experiment 2 but then reduced at day 10. Therefore, HSP47 appears after a period of certain activities to repair damaged collagen fibers, and the activity was returned to a state of equilibrium at day 30 with significantly diminished expression. Thus, the results suggest that HSP47 is actively involved in homeostasis of periodontal tissue subjected to occlusal overload.

Levels of interleukin IL-6 in gingival fluid during orthodontic tooth movement: Children vs. adult

During orthodontic tooth movement comes to remodeling of periodontal ligament and alveolar bone in response to mechanical loading. Mechanical loading, which comes from the orthodontic force causes aseptic inflammatory reaction within the periodontal tissue, which, in turn, initiates the biological processes associated with bone remodeling. As one of the controllers of the process of bone remodeling, during orthodontic treatment, it is mentioned to be interleukin-6 (IL-6). IL-6 stimulates the production of osteoclasts, ie. induces bone resorption to the osteoclastogenesis. The aim of this study was to investigate the influence of patient age on the production of interleukin-6 (IL-6) during the early stages of orthodontic tooth movement Participants were 10 children (mean age 13 years) and 10 adults (mean age 20 years) in which the orthodontic separator placed between the second premolar and first molar on one side and the opposite side served as controls. Samples were taken from treated and control teeth and before 24, 72, and 168 hours of placing the separator. Level of cytokines was determined by means of enzyme-linked whales. The content of IL-6 in gingival fluid of children and adults are remarkably different, when it comes to control, and when it comes to orthodontic treated teeth. IL-6 in gingival fluid control teeth of children was significantly lower than the content of cytokines in gingival fluid control adults. However, during orthodontic treatment, the content of IL-6 in gingival fluid is remarkably increased in children than in adults, in the comparative periods, where the trend changes in the content of this cytokine was the same in children and adults. The degree of increase is higher in children than adults which shows that the immune system of children reacts more quickly to local changes and the metabolic activity of periodontal ligament higher than in adult patients.

Residents' journal review

Residents' journal review

Combined effect of photobiomodulation with a matrix metalloproteinase inhibitor on the rate of relapse in rats.

To investigate combined effect of photobiomodulation with a matrix metalloproteinase (MMP) inhibitor on the relapse rate in relation to MMP expression in rats. Fifty-two rats were divided into four groups according to the treatment modality: control group, irradiation group, doxycycline group, and irradiation with doxycycline group. During a relapse period of 5 days after orthodontic movement, maxillary central incisors were treated by low-level laser therapy (LLLT) as a photobiomodulation and/or doxycycline as a synthetic MMP inhibitor. Relapse rate was evaluated in association with MMP expression at the gene and protein levels. Relapse rates were increased by LLLT (1.57-fold) and decreased by doxycycline (0.83-fold) compared with the control, showing positive correlation with the levels of expression for all MMPs in the periodontal ligament (PDL). LLLT concomitant with doxycycline administration resulted in no significant differences of relapse rate and MMP expression from the control. The combined effect of photobiomodulation with an MMP inhibitor around the relapsing teeth proved to be antagonistic to PDL remodeling activity during relapse. This study suggests a basis for developing a novel biologic procedure targeting the MMP-dependent PDL remodeling to control the relapse rate.