Elastic modulus determination at different levels of periodontal ligament in nanoindentation

In order to investigate the material properties ofperiodontal ligament （ PDL） in different locations, the nanoindentation method is used to survey the elastic modulus of the PDL at different levels. Cadaveric specimens of human mandibular canine were obtained from 4 adult donors, 16 transverse specimens were made from the sections of cervical margin, midroot and apex using the slow cutting machine. The prepared specimens were tested in different sections （along the longitudinal direction） and different areas （in the circumferential direction）. According to the Oliver-Phair theory, the mean values of elastic modulus were calculated foreach area and the differences among them were compared. In the midroot section, the average elastic modulus is ranging from 0. 11 to 0. 23 MPa, the changing range of the cervical margin and apex are from 0. 21 to 0. 53 MPa and 0. 44 to0.62 MPa, respectively. Experimental results indicate that the average elastic modulus in the midroot is lower than that in the cervical margin and apex, and relatively small changes occur among them. However, there is a large change to the elastic modulus value in the cicumferential direction for the PDL.

Therapeutic potential of periodontal ligament stem cells

Inflammatory periodontal disease known as periodontitis is one of the most common conditions that affect human teeth and often leads to tooth loss.Due to the complexity of the periodontium,which is composed of several tissues,its regeneration and subsequent return to a homeostatic state is challenging with the therapies currently available.Cellular therapy is increasingly becoming an alternative in regenerative medicine/dentistry,especially therapies using mesenchymal stem cells,as they can be isolated from a myriad of tissues.Periodontal ligament stem cells(PDLSCs)are probably the most adequate to be used as a cell source with the aim of regenerating the periodontium.Biological insights have also highlighted PDLSCs as promising immunomodulator agents.In this review,we explore the state of knowledge regarding the properties of PDLSCs,as well as their therapeutic potential,describing current and future clinical applications based on tissue engineering techniques.

Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers

Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations： CD51/CD140a, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells （DMSCs） from heterogeneous periodontal ligament cells （PDLCs）. Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51＋/CD140a＋, 0.8% were CD271＋, and 2.4% were STRO-1＋/CD146＋. Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271＋ DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.

Expression analysis of a-smooth muscle actin and tenascin-C in the periodontal ligament under orthodontic loading or in vitro culture

α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament （PDL） under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 （TGF-β1） and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells （hPDLCs）. The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.

Low-power laser irradiation promotes the proliferation and osteogenic differentiation of human periodontal ligament cells via cyclic adenosine monophosphate

Retaining or improving periodontal ligament （PDL） function is crucial for restoring periodontal defects. The aim of this study was to evaluate the physiological effects of low-power laser irradiation （LPLI） on the proliferation and osteogenic differentiation of human PDL （hPDL） cells. Cultured hPDL cel Is were irradiated （660 nm） daily with doses of O, 1, 2 or 4 J .cm-2. Cell proliferation was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide （MTT） assay, and the effect of LPLI on osteogenic differentiation was assessed by Alizarin Red S staining and alkaline phosphatase （ALP） activity. Additionally, osteogenic marker gene expression was confirmed by real-time reverse transcription-polymerase chain reaction （RT-PCR）. Our data showed that LPLI at a dose of 2 J.cm-2 significantly promoted hPDL cell proliferation at days 3 and 5. In addition, LPLI at energy doses of 2 and 4 J.cm-2 showed potential osteogenic capacity, as it stimulated ALP activity, calcium deposition, and osteogenic gene expression. We also showed that cyclic adenosine monophosphate （cAMP） is a critical regulator of the LPLI-mediated effects on hPDL cells. This study shows that LPLI can promote the proliferation and osteogenic differentiation of hPDL cells. These results suggest the potential use of LPLI in clinical applications for periodontal tissue regeneration.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance the Osteoblastic Differentiation of Periodontal Ligament Stem Cells Under High Glucose Conditions Through the PI3K/AKT Signaling Pathway

Objective High glucose(HG)can influence the osteogenic differentiation ability of periodontal ligament stem cells(PDLSCs).Human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSC-exo)have broad application prospects in tissue healing.The current study aimed to explore whether hUCMSC-exo could promote the osteogenic differentiation of hPDLSCs under HG conditions and the underlying mechanism.Methods We used a 30 mmol/L glucose concentration to simulate HG conditions.CCK-8 assay was performed to evaluate the effect of hUCMSC-exo on the proliferation of hPDLSCs.Alkaline phosphatase(ALP)staining,ALP activity,and qRT-PCR were performed to evaluate the pro-osteogenic effect of hUCMSC-exo on hPDLSCs.Western blot analysis was conducted to evaluate the underlying mechanism.Results The results of the CCK-8 assay,ALP staining,ALP activity,and qRT-PCR assay showed that hUCMSC-exo significantly promoted cell proliferation and osteogenic differentiation in a dosedependent manner.The Western blot results revealed that hUCMSC-exo significantly increased the levels of p-PI3K and p-AKT in cells,and the effect was inhibited by LY294002(PI3K inhibitor)or MK2206(AKT inhibitor),respectively.Moreover,the increases in osteogenic indicators induced by hUCMSC-exo were significantly suppressed by LY294002 and MK2206.Conclusion hUCMSC-exo promote the osteogenic differentiation of hPDLSCs under HG conditions through the PI3K/AKT signaling pathway.

Mass acquisition of human periodontal ligament stem cells

The periodontal ligament(PDL)is an essential fibrous tissue for tooth retention in the alveolar bone socket.PDL tissue further functions to cushion occlusal force,maintain alveolar bone height,allow orthodontic tooth movement,and connect tooth roots with bone.Severe periodontitis,deep caries,and trauma cause irreversible damage to this tissue,eventually leading to tooth loss through the destruction of tooth retention.Many patients suffer from these diseases worldwide,and its prevalence increases with age.To address this issue,regenerative medicine for damaged PDL tissue as well as the surrounding tissues has been extensively investigated regarding the potential and effectiveness of stem cells,scaffolds,and cytokines as well as their combined applications.In particular,PDL stem cells(PDLSCs)have been well studied.In this review,I discuss comprehensive studies on PDLSCs performed in vivo and contemporary reports focusing on the acquisition of large numbers of PDLSCs for therapeutic applications because of the very small number of PDLSCs available in vivo.

Effects of Aging on the Proliferation and Differentiation Capacity of Human Periodontal Ligament Stem Cells

periodontal ligament stem cells; aging; proliferation; osteogenic differentiation Objective The aim of this study is to investigate the proliferation, differentiation and apoptosis of periodontal ligament stem cells （PDLSC） derived from different aged donors, and to evaluate the effects of aging on the biological characteristics of PDLSC. Methods Periodontal ligament tissues were obtained from 24 surgically extracted human premolars during orthodontics therapy. The specimens were divided into three groups according to the donor’s age. Group A： 18-20 years, group B： 30-35 years, group C： 45-50 years. PDLSC were isolated and cultured using a tissue-block-based enzymolytic method by limiting dilution assay. The colony forming efficiency of PDLSC for three experimental groups was determined. Senescence-Associated β-Galactosidase （SA-β-G） expression in the three groups was examined using β-galactosidase staining working solution. Cell cycle and apoptosis of the PDLSC were examined by the flow cytometry. Alkaline phosphatase （ALP） activity was evaluated by ALP staining. The expression of osteoplastic differentiation related genes Runt-related transcription factor-2 （Runx-2）, Collagen Type 1 （col-1）, and ALP of PDLSC were examined by quantitative real-time RT-PCR. Results The colony forming efficiency of PDLSC in Group A, B and C was 36.67%, 22.67% and 9.33%, respectively, which decreased with donors’ age （P〈0.05）. SA-β-G expression of the senescent PDLSC in group A, B and C were 4.14%, 16.39%, 50.38%, respectively （P〈0.05）. Cells in G2/S phase was 38.73%, 29.88%, 18.25% （P〈0.05）, and the apoptosis rate was 1.57%, 4.56%, 5.84% （P〈0.05）, in group A, B and C respectively. The ALP staining in the three groups decreased with the increase of donors’ ages, and the expression of Runx-2, col-1 and ALP decreased gradually from group A to group C （all P〈0.05）, which indicated the osteogenic differentiation capacity of PDLSC decreased while donor aging. Conclusion Human PDLSC could be successfully isolated from periodontal ligament tissues of different aged donors. However, the proliferation and osteogenic differentiation capacity of PDLSC decreased while donor aging.

Human periodontal ligament stem cells repair mental nerve injury

Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous Schwann cells in promoting the regeneration of injured peripheral nerve. To validate this hypothesis, human periodontal ligament stem cells （1 × 106） were injected into the crush-injured left mental nerve in rats. Simultaneously, autologous Schwann cells （1 × 106） and PBS were also injected as controls. Real-time reverse transcriptase polymerase chain reaction showed that at 5 days after injection, mRNA expression of low affinity nerve growth factor receptor was sig-nificantaly increased in the left trigeminal ganglion of rats with mental nerve injury. Sensory tests, histomorphometric evaluation and retrograde labeling demonstrated that at 2 and 4 weeks after in-jection, sensory function was significantly improved, the numbers of retrograde labeled sensory neurons and myelinated axons were significantly increased, and human periodontal ligament stem cells and autologous Schwann cells exhibited similar therapeutic effects. These findings suggest that transplantation of human periodontal ligament stem cells show a potential value in repair of mental nerve injury.

Effectiveness and Safety of Computer-controlled Periodontal Ligament Injection System in Endodontic Access to the Mandibular Posterior Teeth

Objective To evaluate the effectiveness and safety of a computer-controlled periodontal ligament （PDL） injection system to the local soft tissues as the primary technique in endodontic access to mandibular posterior teeth in patients with irreversible pulpitis. Methods A total of 162 Chinese patients who had been diagnosed with irreversible pulpitis in their mandibular posterior teeth without acute infection or inflammation in the periodontal tissues were enrolled in this clinical study. The patients were divided into 3 groups according to the position of the involved tooth： the premolar group （PM, z2=38）, first molar group （FM, n=66）, and second molar group （SM, n=58）. All the patients received computer-controlled PDL injection with 4% articaine and 1 ＇ 100 000 epinephrine. Immediately after the injection, endodontic access was performed, and the degree of pain during the treatment was evaluated by the patients using Visual Analogue Scale for pain. The success rates were compared among the 3 groups. The responses of local soft tissues were evaluated 3-8 days and 3 weeks after the procedure. Results The overall success rate was 76.5%. There was a significant difference in success rates among the PM, FM, and SM groups （92.1%, 53.0%, 93.1%, respectively; 2 X =34.3, P〈0.01）. Both the PM and SM groups showed higher success rates than that of the FM group （v=l, f=16.73, P〈0.01, v=l, Z = 4.5, X2 2 P〈0.01）. No irreversible adverse effects on the periodontal soft tissues at the injection sites were observed in the follow-up visits in any of the groups. Conclusion The computer-controlled PDL injection system demonstrates both satisfactory anesthetic effects and safety in local soft tissues as primary anesthetic technique in endodontic access to the mandibular posterior teeth in patients with irreversible pulpitis.

Triclosan inhibits the activation of human periodontal ligament fibroblasts induced by lipopolysaccharide from Porphyromonas gingivalis

Periodontitis is a highly prevalent,chronic,non-specific,and immunologically devastating disease of periodontal tissues,caused by microbial infection.This study aims to examine the efficacy and protective mechanism of triclosan(TCS),a bisphenolic,non-cationic component of oral care products,against periodontal inflammation induced by lipopolysaccharide purified from Porphyromonas gingivalis(LPS-PG).TCS markedly downregulated interleukin-6(IL-6),IL-8,and IL-15 in human periodontal ligament fibroblasts(HPDLFs)treated with LPS-PG.By using a liquid chromatography-tandem mass spectrometry(LC-MS/MS)approach,318 differentially expressed proteins(161 upregulated and 157 downregulated)were identified in TCS-pretreated HPDLFs.TCS upregulated HSPA5 and HSP90B1 but downregulated HSPA2.Besides,TCS upregulated miR-548i in HPDLFs,which downregulated IL-15.These results indicate that TCS attenuates the activation of HPDLFs and downregulates the inflammatory cytokines through various mechanisms,thus highlighting its protective role in periodontal inflammation.

The biomechanical role of periodontal ligament in bonded and replanted vertically fractured teeth under cyclic biting forces

After teeth are replanted,there are two possible healing responses：periodontal ligament healing or ankylosis with subsequent replacement resorption.The purpose of this study was to compare the fatigue resistance of vertically fractured teeth after bonding the fragments under conditions simulating both healing modes.Thirty-two human premolars were vertically fractured and the fragments were bonded together with Super-Bond C＆B.They were then randomly distributed into four groups（BP,CP,CA,BA）.The BP and CP groups were used to investigate the periodontal ligament healing mode whilst the BA and CA groups simulated ankylosis.All teeth had root canal treatment performed.Metal crowns were constructed for the CP and CA groups.The BP and BA groups only had composite resin restorations in the access cavities.All specimens were subjected to a 260 N load at 4 Hz until failure of the bond or until 2 x 106 cycles had been reached if no fracture occurred.Cracks were detected by stereomicroscope imaging and also assessed via dye penetration tests.Finally,interfaces of the resin luting agent were examined by scanning electron microscope.The results confirmed that the fatigue resistance was higher in the groups with simulated periodontal ligament healing.Periodontal reattachment showed important biomechanical role in bonded and replanted vertically fractured teeth.

Effects of Apatite Nanocrystals on Proliferation, Subcellular Structure, Protein Synthesis Activity of Human Periodontal Ligament Cells

To determine the cellular events occurring in the presence of yttrtum/ hyclroxyapatite（Y / HA ） or HA nanocrystals, human periodontal ligament （HPDL） cells were isolated and maintained in culture. The specificity of the cells was evidenced by their proliferation, subcellular structure, and deposition of extracellular matrix components. The presence of nanocrystals was significantly related to an increase in the proliferation. Moreover, the presence of Y/HA nanocrystals was significantly related to an increase in the proliferation with HA nanocrystals. Transmission electron microscopy （TEM） demonstrated the phagocytotic process of HPDL cells toward Y/ HA or HA nanocrystuls . The presence of Y/ HA or HA nanocrystuls was significantly related to an increase in the protein synthesis activity of HPDL cells.

Influence of baicalin on the expression of receptor activator of nuclear factor-κB ligand and osteoprotegerin in human periodontal ligament cells

Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering RNA(siRNA)eukaryotic expression vector targeted transforming growth factor βⅡ receptor(TGF-β RⅡ)was constructed and transfected into T cells.HPDL cells with T cells transfected with siRNA or not were placed in the culture medium that had been added with lipopolysaccharide(LPS)and baicalin.The obtained solution was divided into six groups according to the components(group Ⅰ:HPDL cells+LPS+T cells transfected with siRNA1+baicalin;group Ⅱ:HPDL cells+LPS+T cells transfected with siRNA1;group Ⅲ:HPDL cells+LPS+T cells+baicalin;group Ⅳ:HPDL cells+LPS+T cells;group Ⅴ:HPDL cells+baicalin;group Ⅵ:HPDL cells)and was cultured for 48 hours.RT-PCR was used to observe the effect of baicalin on the expression of OPG-RANKL in HPDL cells.Results The ratio of RANKL/OPG in group Ⅰ was lower than that in group Ⅱ(P<0.01)and higher than that in group Ⅲ(P<0.01);The ratio of RANKL/OPG in group Ⅲ was lower than that in group Ⅳ(P<0.01);the ratio of RANKL/OPG in group Ⅳ was higher than that in group Ⅵ(P<0.01);the ratio of RANKL/OPG in group Ⅴ was lower than that in group Ⅵ(P<0.05).Conclusion ① Baicalin could decrease the ratio of RANKL/OPG in HPDL cells.② The TGF-β signaling transduction plays an important role in the effect of baicalin on the RANKL/OPG ratio in HPDL cells.③ Baicalin acts not only through TGF-β to regulate RANKL/OPG in HPDL cells,but also through other pathways.

The Effects of Dense/Nanometer Hydroxyapatite on Proliferation and Osteogenetic Differentiation of Periodontal Ligament Cells

The objective of this study is to investigate possible effects of nanometer powder of hydroxyapatite on proliferation of periodontal ligament cells. With sol-gel method, the nanometer hydroxyapatite powder were fabricated. The primary periodontal ligcament cells were caltured on dense particle hydroxyapatite and nanometer particle hydroxyapatite. The effects on proliferation of periodontal ligament cell were examined in vitro with MTT （ methyl thiazolil tetracolium） test. The intercellalar effects were observed with scanning electron microscopy and energy dispersive X-ray analyzer. In addition, the influence of two materials on osteogenetic differentiation was determined with measurement of ALP （ alkaline phosphatase ） activity. It is concluded that nanometer hydroxyapatite can promote proliferation and osteogenetic differeraiation of periodontal ligament cells and it may become absorbable agent in osseous restoration.

Cell Attachment of Periodontal Ligament Cells on Commercially Pure Titanium at the Early Stage

Summary: In order to study the character of periodontal ligament cells (PDLCs) attaching on commercially pure titanium (cpTi) by morphology and metrology on the early stage (24 h), 1×105/ml PDLCs in 2 ml culture medium were seeded on cpTi discs fixed in 24-well culture plates. Morphology of cell attachment was observed by contrast phase microscope, scanning electron microscope (SEM) and fluroscence microscopy. Cell adhesion was analyzed by MTT at 0.5, 1, 2, 4 h respectively. PDLCs could attach and spread on cpTi discs. SEM showed that PDLCs had pseudopod-like protuberance. PDLCs showed different attaching phases and reached saturation in cell number at 2 h. It was concluded that PDLCs had good biocompatibility with cpTi, and showed a regular and dynamic pattern in the process of attaching to cpTi.

Stretching Induces the Rearrangement of the Periodontal Ligament Cells without Altering the Orientation of Oxytalan Fibers Relative to the Cell Axis in Vitro

The periodontal ligament (PDL) contains oxytalan fibers as well as collagen fibers, which helps it to withstand the mechanical stress to which it is constantly exposed. The oxytalan fibers are produced by PDL fibroblasts. However, the arrangement of PDL fibroblasts and the orientation of oxytalan fibers relative to the fibroblast cell axis have not been investigated under the condition of mechanical stress. We hypothesized that such stress would alter the arrangement and orientation of these cells and their oxytalan fibers. The aim of this study was to evaluate the effects of stretching strain on PDL fibroblasts, focusing on the cellular arrangement and orientation of oxytalan fibers relative to the long cell axis in cell/matrix layers by staining the major component of the fibers, fibrillin-1. The angle between the long cell axis and the oxytalan fibers was approximately 70 degrees under both non-stretching and stretching conditions. Moreover, stretching induced the rearrangement of the cells. This is the first study to demonstrate that stretching induces the rearrangement of the PDL fibroblasts without altering the angle between the long cell axis and the oxytalan fibers. These results may reflect the orientation of oxytalan fibers in the PDL under the condition of mechanical stress.

The Effect of Phosphatase and Tension Homolog (PTEN) on Homeostasis of the Periodontal Ligament

Aim: Phosphatase and tension homolog (PTEN) has been known to maintain homeostatic control over the body. The roles of PTEN in periodontal complex are unknown. The purpose of this study was to investigate the role of PTEN in periodontal structures by removing PTEN from osteoblasts and odontoblasts. Materials and Methods: The function of this endogenous PTEN was evaluated by conditionally eliminating the PTEN gene using an Osteocalcin (OCN) Cre driver. The resulting OCN-Cretg/+;Ptenfl/fl mice were examined using micro-CT and histology, immunohistochemical analyses for osteogenic markers in the periodontal ligament (PDL) and bone turnover. Results: Bone apposition was increased around molar areas accompanying deposition of cementum in micro CT. Osteoprogenitor markers except for OCN in the PDL maintained their expression in both wild-type and OCN-Cretg/+;Ptenfl/fl mice. Both alkaline phosphatase activity and osteoclast activity increased in the PDL of OCN-Cretg/+;Ptenfl/fl mice compared to those in wild-type mice. Conclusions: Loss of PTEN causes an increase of bone turnover in the periodontal surrounding tissues with an increase of cementogenesis. These findings underscore the effect of PTEN on homeostasis of the periodontal ligament.

EFFECTS OF TRANSFORMING GROWTH FACTOR β AND RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN 2 ON HUMAN PERIODONTAL LIGAMENT FIBROBLASTS

Objective To evaluate the effects of transforming growth factor β(TGF-β) and recombinant human bone morphogenetic protein 2 (rhBMP2) on human periodontal ligament fibroblasts (HPDLFs). Methods HPDLFs were done primary culture to detect the distinct concentrations of TGF-P and rhBMF2 on its proliferation, alkaline phosphatase (ALP) activity, osteocalcin (OC) synthesis and formation of the minerali-zed nodules, respectively. Results TGF-β (5～100ng/ml) significantly stimulated the proliferation of HPDLFs. The ALP activity of HPDLFs was evaluated evidently by 5ng/ml TGF-β. TGF-β( 0. 5 ～ 100ng/ml) had no effects on OC synthesis and formation of the mineralized nodules of HPDLFs. rhBMP2 (0. 25～2mg/ ml) had no remarkable effect on the proliferation of HPDLFs. The ALP activity, OC synthesis and forma-tion of the mineralized nodules of HPDLFs were significantly stimulated by 0. 5～ 2mg /ml rhBMP2. Conclusion The effects of TGF-β and rhBMP2 on HPDLFs are dose-dependent. TGF-P can stimulate HPDLFs to express the early marker of osteoblastic phenotype, and it lacks the ability to promote maturation of the osteogenic phenotype. rhBMP2 can not only stimulate the expression but also promote the maturation of osteoblas-tic phenotype of HPDLFs.

Overview of the main biological mechanisms linked to changes in periodontal ligament stem cells and the inflammatory microenvironment

Periodontitis is a complex chronic inflammatory disease.The invasion of pathogens induces the inflammatory microenvironment in periodontitis.Cell behavior changes in response to changes in the microenvironment,which in turn alters the local inflammatory microenvironment of the periodontium through factors secreted by cells.It has been confirmed that periodontal ligament stem cells(PDLSCs)are vital in the development of periodontal disease.Moreover,PDLSCs are the most effective cell type to be used for periodontium regeneration.This review focuses on changes in PDLSCs,their basic biological behavior,osteogenic differentiation,and drug effects caused by the inflammatory microenvironment,to provide a better understanding of the influence of these factors on periodontal tissue homeostasis.In addition,we discuss the underlying mechanism in detail behind the reciprocal responses of PDLSCs that affect the microenvironment.