Excessive Orthodontic Force Research Articles

Dual role of Sfrp4 in bone remodelling during orthodontic tooth movement.

The objective of this study was to determine changes in gene expression by establishing an orthodontic tooth movement (OTM) rat model with appropriate and excessive orthodontic force. Using a closed coil nickel-titanium spring, the OTM was carried out to apply a mesial force of 50 or 100 g to the maxillary first molars. Micro-CT, histological and immunohistochemical staining were used to evaluate the bone formation at the tension site and the bone resorption and bone formation at pressure site. Then RNA sequencing and bioinformatic analysis were performed. According to the results of the Mirco-CT scan of OTM rat models, both the 50 g group and the 100 g group showed variable degrees of reduction in alveolar bone density on the tension and pressure sides. The results of histological and immunohistochemical staining demonstrated that the periodontal tissue and osteogenic ability of the 50 g group were restored at the 14 days, while the 100 g group caused severe periodontal tissue damage. The GO and KEGG analysis results, as well as the number of differentially expressed genes (DEGs), varied depending on the loading time and value of appliance, according to the results of the RNA sequencing. And the immunohistochemical staining results showed that Sfrp4 functioned by efficiently influencing both bone formation and bone absorption. Appropriate orthodontic force value could cause appropriate movement of teeth in rats without adverse periodontal damage. Simultaneously, distinct gene expression patterns were observed at various force levels and time intervals.

Effect of low-intensity pulsed ultrasound on the mineralization of force-treated cementoblasts and orthodontically induced inflammatory root resorption via the Lamin A/C-Yes associated protein axis.

Orthodontic treatment commonly results in orthodontically induced inflammatory root resorption (OIIRR). This condition arises from excessive orthodontic force, which triggerslocal inflammatory responses and impedes cementoblasts' mineralization capacity. Low-intensity pulsed ultrasound (LIPUS) shows potential in reducing OIIRR. However, the precise mechanisms through which LIPUS reduces OIIRR remain unclear. This study aimed to explore the effects and mechanisms of LIPUS on the mineralization of force-treated cementoblasts and its impact on OIIRR. We established a rat OIIRR model and locally administered LIPUS stimulation for 7 and 14 days. We analyzed root resorption volume, osteoclast differentiation, and the expression of osteocalcin and yes-associated protein 1 (YAP1) using micro-computed tomography (micro-CT), hematoxylin and eosin, tartrate-resistant acid phosphatase, immunofluorescence and immunohistochemistry staining. Invitro, we applied compressive force and LIPUS to the immortalized mouse cementoblasts (OCCM30). We assessed mineralization using alkaline phosphatase (ALP) staining, alizarin red staining, real-time quantitative polymerase chain reaction, Western blotting and immunofluorescence staining. In rats, LIPUS reduced OIIRR, as evidenced by micro-CT analysis and histological staining. Invitro, LIPUS enhanced mineralization of force-treated OCCM30 cells, as indicated by ALP and alizarin red staining, upregulated mRNA expression of mineralization-related genes, and increased protein expression of mineralization markers. Mechanistically, LIPUS activated YAP1 signaling via the cytoskeleton-Lamin A/C pathway, supported by immunofluorescence and Western blot analysis. This study demonstrates that LIPUS promotes mineralization in force-treated cementoblasts and reduces OIIRR by activating YAP1 through the cytoskeletal-Lamin A/C signaling pathway. These findings provide fresh insights into how LIPUS benefits orthodontic treatment and suggest potential strategies for preventing and treating OIIRR.

Effect of Orthodontic Treatment on Endodontically Treated Teeth

ABSTRACT Background: This research has been conducted to assess the effect of orthodontic treatment on endodontically treated tooth. Materials and Methods: Overall, fifty subjects had been recruited. The participants received root canal therapy within 3 months as well as had an appointment for fixed orthodontic therapy. All candidates underwent an intraoral investigation. Radiographic evaluation as well as therapy planning were completed. Fixed orthodontic therapy had been initiated. All of the participants had been recalled. Endodontically restored teeth had been evaluated. All outcomes were assessed via Statistical Package for the Social Sciences (SPSS) software. Results: In this study, there were 25 males and 25 females. Pulp stones were seen in 15 subjects. Apical periodontitis was seen in nine subjects. Apical root resorption was seen in seven subjects, and enamel decalcification was seen in four subjects. Overall, 35 out of 50 subjects showed negative effects of orthodontic treatment on endodontically treated teeth. Conclusion: Excessive orthodontic force may result in increased pulp and peri-apical inflammation.

The Hydrostatic Pressure Distribution in the Periodontal Ligament and the Risk of Root Resorption-A Finite Element Method (FEM) Study on the Nonlinear Innovative Model.

Excessive orthodontic force can induce inflammatory tooth root resorption due to sustained high stresses within the periodontal ligament (PDL). This study aimed to analyze the PDL pressures during upper incisor retraction using the en masse method with TISAD. The finite element method (FEM) ensured consistent conditions across cases. The models included bone geometry, adjacent teeth, PDL, and orthodontic hardware, analyzed with LS-Dyna. The pressure ranged from 0.37 to 2.5 kPa across the dental arch, with the central incisors bearing 55% of the load. The pressure distribution remained consistent regardless of the force or hook height. The critical pressure (4.7 kPa) was exceeded at 600-650 g force, with notable pressure (3.88 kPa) on the palatal root wall of the right central incisor. Utilizing 0.017 × 0.025 SS archwires in MBT 0.018 brackets provided good torque control and reduced the root resorption risk when forces of 180-200 g per side were applied, maintaining light to moderate stress. Triple forces may initiate resorption, highlighting the importance of nonlinear finite element analysis (FEA) for accurate oral cavity simulations.

Stem cells derived from human exfoliated deciduous teeth-based media in a rat root resorption model

ObjectiveRoot resorption may occur during orthodontic treatment. Herein, we investigated the effect of a culture supernatant of stem cells derived from human exfoliated deciduous teeth on root resorption. DesignTwelve 8-week-old male Sprague–Dawley rats were used, and their maxillary first molars were pulled with excessive orthodontic force to induce root resorption. On days 1 and 7 after traction initiation, stem cells derived from human exfoliated deciduous teeth and alpha minimum essential medium (control group) were administered. After 14 days, the maxillary bone was evaluated for tooth movement. The expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1β, interleukin 6, and interleukin 17 was evaluated on the compression side and tension side. ResultsNo significant difference in tooth movement was observed between the two groups. Root resorption decreased in the group administered the culture supernatant compared with in the control. Immunohistochemical staining revealed increased osteoprotegerin expression and decreased receptor activators for nuclear factor κB ligand, tumor necrosis factor α, interleukin 1β, interleukin 6, and interleukin 17 on the compression side and tension side. ConclusionsAdministration of stem cells derived from human exfoliated deciduous teeth affected the expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1β, interleukin 6 and interleukin 17; hence, these stem cells may inhibit root resorption by regulating their expression.

Mechanisms of sphingosine-1-phosphate (S1P) signaling on excessive stress-induced root resorption during orthodontic molar intrusion.

The aim of this study was to investigate cementocyte mechanotransduction during excessive orthodontic intrusive force-induced root resorption and the role of S1P signaling in this process. Fifty-four 12-week-old male Wistar rats were randomly divided into 3 groups: control group (Control), intrusive stress application group (Stress), and intrusive stress together with S1PR2-specific antagonist injection group (Stress + JTE). A rat molar intrusion model was established on animals in the Stress and the Stress + JTE groups. The animals in the Stress + JTE group received daily intraperitoneal (i.p.) injection of S1PR2 antagonist JTE-013, while the Control and Stress groups received only the vehicle. Histomorphometric, immunohistochemical, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses were performed after euthanizing of the rats. Root resorption was promoted in the Stress group with increased volumes of resorption pits and amounts of molar intrusion compared with the Control group. The expression levels of cementogenic- and cementoclastic-related factors were affected under excessive intrusive force. Immunohistochemical staining and qRT-PCR analysis showed promoted S1P signaling activities during molar intrusion. Western blot analysis indicated decreased nuclear translocation of β-catenin under excessive intrusive force. Through the administration of JTE-013, S1P signaling activity was suppressed and excessive intrusive force-induced root resorption was reversed. The regulation of S1P signaling could also influence the nuclear translocation of β-catenin and the expressions of cementogenic- and cementoclastic-related factors. Root resorption was promoted under excessive orthodontic intrusive force due to the disruption of cementum homeostasis. S1P signaling pathway might play an important role in cementocyte mechanotransduction in this process. The S1P signaling might be a promising therapeutic target for novel therapeutic approaches to prevent external root resorption caused by excessive orthodontic intrusive force.

Inhibitory Effects of 4-Hexylresorcinol on Root Resorption Induced by Orthodontic Tooth Movement

Root resorption during orthodontic tooth movement (OTM) is caused by an imbalance between the bone turnover rate and applied mechanical stress. The administration of 4-hexylresorcinol (4HR) increases the bone turnover rate and factors associated with bone formation. Thus, 4HR may show protective activity against root resorption during orthodontic tooth movement (OTM). A total of 40 rats (male: 20; female: 20) were included in this study, and the mandibular first molar was subjected to excessive orthodontic force. The experimental group (n = 20) received 12.8 mg/kg of 4HR every 2 weeks. The controls (n = 20) received a solvent without 4HR. Both groups had the same sex distribution. On Day 28 after the initiation of OTM, all the animals were sacrificed for micro-computed tomography analysis, Western blot analysis, and immunohistochemistry. The ratios of the root length and root volume to the total volume were significantly higher in the experimental group compared to those in the control group (p < 0.05). The expression levels of OPG, RANKL, alkaline phosphatase, and Runx2 in the experimental group according to Western blotting were significantly higher in the experimental group compared to those in the control group (p < 0.05). Their expression was mainly found in the periodontal ligament area. In conclusion, the administration of 4HR decreased the root resorption caused by OTM and increased the expression levels of OPG, RANKL, alkaline phosphatase, and Runx2.

Baicalin inhibits root resorption during tooth movement in a rodent model

ObjectiveBaicalin mediates bone metabolism and has shown protective activity against periodontal tissue damage in a rat model of periodontitis. Therefore, we hypothesized that baicalin may inhibit the root resorption that occurs during orthodontic tooth movement and examined its effect on the histological changes in periodontal tissue that occur during tooth movement. MethodsFirst molars of rats were subjected to traction using excessive orthodontic force to produce a root resorption model. Rats in the baicalin group received baicalin for 3 weeks during tooth movement, and the amount of first molar movement on day 21 after the initiation of traction was measured by three-dimensional micro-computed tomography analysis. After tooth movement, tissue samples from the mesial and tension sides were collected, and successive horizontal sections were prepared and examined using hematoxylin–eosin and tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical staining for the receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG). The severity of root resorption was also determined by histological analysis. ResultsThere was no significant intergroup difference in tooth movement during the experimental exaggerated tooth movement. In comparison with the control group, the baicalin-treated group showed increased OPG expression, suppressed RANKL expression, and significantly fewer TRAP-positive cells in the first molars. The root resorption area was significantly smaller in the baicalin group. ConclusionsTreatment with baicalin prevented root resorption without preventing tooth movement. Baicalin may be useful for the management of root resorption during orthodontic treatment.

NLRP3 inflammasome mediates M1 macrophage polarization and IL-1β production in inflammatory root resorption.

To explore the involvement of NOD-like receptor protein 3 (NLRP3) inflammasome and M1 macrophage in root resorption (RR). A rat RR model was established by excessive orthodontic force. After different force-loading time, the expression levels of NLRP3, caspase-1, and interleukin-1β (IL-1β) and distribution of M1 macrophages were analysed by immunohistochemistry and immunofluorescence staining in vivo. Then, the mechanism of NLRP3 activation was further verified by macrophage and human periodontal ligament cell (hPDLC) co-culture system in vitro. The production levels of NLRP3, caspase-1, pro-caspase-1, and IL-1β in M1 macrophages in the co-culture system were detected by Western blot, and the polarization of CD68+IL-1β+ M1 macrophages was detected by immunofluorescence staining. In the rat RR model, NLRP3, caspase-1, IL-1β, and M1 macrophages were expressed in periodontal ligament, mainly concentrated around RR areas. Force-pre-treated hPDLCs promoted M1 macrophage polarization and the production of NLRP3, caspase-1, and IL-1β in M1 macrophages in co-culture system. When MCC950, an inhibitor of NLRP3 inflammasome, was added, NLRP3 activation and M1 macrophage polarization were inhibited. In periodontal tissues, hPDLCs stimulated by force promoted M1 macrophage polarization and increased IL-1β production by activating NLRP3 inflammasome in M1 macrophages, thus initiating the occurrence of RR.

Finite element analysis of orthodontically induced stress in the periodontal ligament of the maxillary first molar with simulated bone loss

The problems that often arises in orthodontic treatment of adult patients is the presence of periodontal disease and loss of bone support. As a consequence of this, the center of resistance of the tooth is altered. Excessive orthodontic force with advanced periodontal bone loss may traumatize the p eriodontium. Force dosage during orthodontic treatment is one of the most difficult problems at this stag.the purpose of the study is to simulate the effect of orthodontically induced stress in the periodontal ligament of maxillary molar at different levels of bone loss. The study is carried out to estimate the reduction in magnitude of force at different levels of bone loss (2.5 mm, 5 mm and 6.5 mm) necessary to achieve evenly distribution of stress in the periodontal ligament of the tooth as obtained without bone loss and to determine the change in counterbalancing M/F ratio to induce uniform stress distribution in the PDL. A 3-dimensional finite element model of a tooth comprises of maxillary first molar with periodontal ligament and alveolar bone with different levels of bone height was constructed. Bone loss that ranged from 2.5 thrugh 6.5 mm was simulated in a model. Necessary reduction in the magnitude of force and the increase in moment to force (M/F) ratio was determined to obtain evenly distributed stress in the periodontal ligament of a tooth. The results showed that lesser force magnitude is required in simulated 2.5 mm bone loss (80%), 5 mm bone loss (60%), 6.5 mm bone loss (35%) as compared to the initial load applied to the tooth without bone loss. The counter tipping moment to force ratio should be increased from no bone loss (9.65) through 6.5 mm bone loss (12.8) to maintain the same range of stress in the PDL as was obtained without bone loss. The counter rotation moment to force ratio should decrease from no bone loss (5.65) through 6.5 mm bone loss (4.0) to maintain the same range of stress in the PDL as was obtained without bone loss. Combination of decreased force magnitude and increased counter tipping moment to force ratio will bring about uniform stress in the periodontal ligament of a tooth with varying degree of bone loss.

<b>Expression of IL-34 in Root Resorption by Excessive Orthodontic Force </b>

<b>Expression of IL-34 in Root Resorption by Excessive Orthodontic Force </b>

Histomorphometric analysis of overloading on palatal tooth movement into the maxillary sinus.

Our objective was to evaluate the effect of overloading on the palatal movement of the maxillary molar. The maxillary first molars of male C57Bl/6 mice were moved palatally with loads of 10 or 30 g for 14 days, and the amount of tooth movement was longitudinally measured on microcomputed tomography images. Bone remodeling around the molar root with the 30-g load was evaluated at days 3, 5, 7, and 14 after the start of tooth movement using histomorphometry and immunodetection of bone-restricted interferon inducible transmembrane-like protein, a novel marker of active bone formation. In the 10-g load group, the amount of tooth movement increased dramatically between days 5 and 7 and increased gradually thereafter. Tooth movement at days 5 and 7 was significantly lower in the 30-g-load group than in the 10-g load group; however, the total tooth movement at 14 days was similar in the 2 groups. An orthodontic load of 30 g stimulated bone formation on the sinus wall, but bone resorption on the periodontal ligament side was delayed because of hyalinization, which means that strong force application did not accelerate tooth movement. Moreover, some root resorption was induced by the excessive force. Root penetration into the sinus and bone height reduction do not occur because new bone formation on the maxillary sinus is induced before bone resorption on the periodontal side, even though an excessive orthodontic force is applied. However, an excessive force can induce root resorption.

Analysis of periapical alveolar bone resorption after the removal of interdental wire ligation

Background/PurposePeriapical bone resorption is mainly induced by inflammation resulting from an infected root canal. However, chemical and physical stimuli (e.g., traumatic occlusions and excessive orthodontic force) can also cause periapical bone resorption. Here, we report the induction of a periapical bone resorption model without infection in rats. MethodsWire ligature was applied between the upper first and second molars for 2 weeks. At 2 weeks and 4 weeks after removal of the wire, the maxillary bones were processed for micro-computed tomography and histological analyses. ResultsThe micro-computed tomography analysis showed that periapical bone resorption had occurred and that the bone volume had significantly decreased between Week 2 and Week 4 after wire removal. Histological examination showed a normal apical periodontal ligament. No accumulation of inflammatory cells and no abscess formation were detected in the periapical region. Meanwhile, many tartrate-resistant acid phosphatase-positive osteoclasts were detected in the periapical region of non-wire-ligated rats in which the dental pulp had been exposed; however, active osteoclasts were still located at the alveolar bone in rats even at 4 weeks after wire removal. ConclusionThese results indicate that induction of periapical bone resorption occurred in the absence of infection and that a bone resorption system different from the infection-associated bone resorption one accounted for the changes.

Interleukin‐17/T‐helper 17 cells in an atopic dermatitis mouse model aggravate orthodontic root resorption in dental pulp

Interleukin (IL)-17 is an important mediator of orthodontically induced inflammatory root resorption (OIIRR). However, its role in the dental pulp (DP) has not been studied. The aim of this study was to investigate, using an atopic dermatitis (AD) model, how IL-17 contributes to OIIRR in DP. Atopic dermatitis is the most common IL-17-associated allergic disease. Atopic dermatitis model mice (AD group) and wild-type mice (control group) were subjected to an excessive orthodontic force. The localization of T-helper (Th)17 cells, IL-17, IL-6, and keratinocyte chemoattractant (KC; an IL-8-related protein in rodents) were determined in DP. In addition, CD4+ T cells, including IL-17 production cells, were obtained from patients with AD and from healthy donors, and the effects of IL-17 on the production of IL-6 and IL-8 were investigated using a co-culture of CD4+ T cells with human dental pulp (hDP) cells stimulated with substance P (SP). Immunoreactivity for Th17 cells, IL-17, IL-6, and KC was increased in DP tissue subjected to orthodontic force in the AD group compared with DP tissue subjected to orthodontic force in the control group. The cells obtained from the AD patients displayed increased IL-6 and IL-8 production. These results suggest that IL-17 may aggravate OIIRR in DP.

Immunohistochemical Localization of T-helper 17 Cells, IL-17, and RANKL during Root Resorption Induced by Excessive Orthodontic Force in the Mouse Model of T Cell-mediated Autoimmune Disease

Immunohistochemical Localization of T-helper 17 Cells, IL-17, and RANKL during Root Resorption Induced by Excessive Orthodontic Force in the Mouse Model of T Cell-mediated Autoimmune Disease

Th17‐cells in atopic dermatitis stimulate orthodontic root resorption

The aim of this study was to investigate how atopic dermatitis (AD) contributes to root resorption during orthodontic tooth movement. Atopic dermatitis model mice and wild-type mice were subjected to an excessive orthodontic force (OF) to induce movement of the upper first molars. The expression levels of the tartrate-resistant acid phosphatase (TRAP), IL-17, IL-6, and RANKL proteins were determined in the periodontal ligament (PDL) by an immunohistochemical analysis. Furthermore, the effects of the compression force on co-cultures of CD4(+) cells from AD patients or healthy individuals and human PDL cells were investigated with regard to the levels of secretion and mRNA expression of IL-17, IL-6, RANKL, and osteoprotegerin. The immunoreactivities for TRAP, IL-17, IL-6, and RANKL in the AD group were found to be significantly increased. The double immunofluorescence analysis for IL-17/CD4 detected immunoreaction. The secretion of IL-17, IL-6, and RANKL, and the mRNA levels of IL-6 and RANKL in the AD patients were increased compared with those in healthy individuals. Th17 cells may therefore be associated with the deterioration of root resorption of AD mice, and may explain why AD patients are more susceptible to root resorption than healthy individuals when an excessive OF is applied.

Partial pulp necrosis caused by excessive orthodontic force

As the dental pulp is encased with a rigid, noncompliant shell, changes in pulpal blood flow or vascular tissue pressure can have serious implication for the health of pulp. Numerous studies have demonstrated that orthodontic force application may influence both blood flow and cellular metabolism, leading degenerative and/or inflammatory responses in the dental pulp. The aim of this case report is to present a case about tooth with chronic periapical abscess which showed normal vital responses. Excessive orthodontic force is thought to be the prime cause of partial pulp necrosis. Owing to remaining vital tissue, wrong dianosis can be made, and tooth falsely diagnosed as vital may be left untreated, causing the necrotic tissue to destroy the supporting tissuses. Clinician should be able to utilize various diagnostic tools for the precise diagnosis, and be aware of the endodontic-orthodontic inter-relationship. [J Kor Acad Cons Dent 2011;36(2):149-153.]

IL‐8 and MCP‐1 induced by excessive orthodontic force mediates odontoclastogenesis in periodontal tissues

The aim of this study was to investigate how interleukin (IL)-8 (cytokine-induced neutrophil chemoattractant; CINC-1) and monocyte chemotactic protein (MCP)-1/CCL2 contribute to root resorption during orthodontic tooth movement. Forty 6-week-old male Wistar rats were subjected to orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars for 7 days. We determined the expressions of CINC-1, CXCR2, and MCP-1 proteins in root resorption area using immunohistochemistry. Furthermore, we investigated the effects of compression forces (CF) on IL-8 and MCP-1 production by human periodontal ligament (hPDL) cells. We observed an effect of chemokine treatment on rat odonto/osteoclasts in dentin slices that recapitulated root resorption. The immunoreactivity for CINC-1/CXCR2 and MCP-1 was detected in odontoclasts and PDL fibroblasts by the orthodontic force of 50 g on day 7. CF increased the secretion and the expression of mRNA of IL-8 and MCP-1 from PDL cells in a magnitude-dependent manner. Moreover, CINC-1 and MCP-1 stimulated osteoclastogenesis from rat osteoclast precursor cells. IL-8 (CINC-1) and MCP-1 may therefore facilitate the process of root resorption because of excessive orthodontic force.

Excessive Orthodontic Force Induces Odontoclastogenesis in Root Cementum as Evidenced by the Expression of RANK/RANKL

The differentiation and functions of osteoclasts are regulated by the receptor activator of nuclear factor kappa beta (RANK) and its ligand (RANKL). The present study was designed to identify the expression of RANK/RANKL in the event of root resorption provoked by excessive orthodontic force and also to explore the biological mechanism of the RANK/RANKL system in regulating odontoclastogenesis in root cementum. Thirty male Wistar rats were subjected to orthodontic force of 100 g to induce a mesially tipping movement of the left mandibular first molars. The contralateral molars served as intraindividual controls. The rats were sacrificed after 3, 7, or 10 days. The mandibular body surrounding the molars was harvested and serial sections of 6-μm thickness were cut. Immunohistochemical assays were conducted to localize the expression of RANK/RANKL proteins and histomorphological examination was undertaken to identify cellular response in cementum, periodontal ligament, and alveolar bone during root resorption. Root resorption in cementum occurred at the sites corresponding to compression of the periodontal ligament, indicated by increased numbers of multinucleated osteoclasts and odontoclasts. Immunoreaction against RANKL became stronger in osteoblasts, osteoclasts, odontoclasts, and fibroblasts of the periodontal ligament from Day 3 onwards. The number of positively immunoreactive cells against RANK also increased significantly over Days 3, 7, and 10 (p<0.01). The RANK/RANKL system is responsible for transducing the heavy mechanical loading signals into an odontoclastic episode in root resorption.

Compressive Force Induces Osteoblast Apoptosis via Caspase-8

Periodontal remodeling during orthodontic tooth movement is a result of mechanical stresses. The application of excessive orthodontic force induces cell death. However, the nature of compressive force-induced cell death is unclear. We examined whether the in vitro application of continuous compressive force would induce apoptosis in human osteoblast-like cells (MG-63 cells), and investigated the mechanism by which apoptosis was initiated. The cells became aligned irregularly, and cell viability decreased, indicating that the compressive force caused cell death. According to the TUNEL analysis, the number of apoptotic cells increased significantly in a time-and force-dependent manner. Caspase-3 activity increased with the magnitude of the compressive force, and this effect was reduced significantly by a caspase-8 inhibitor, whereas a caspase-9 inhibitor had no such effect. We conclude that the in vitro application of compressive force can induce apoptosis in MG-63 cells through the activation of caspase-3 via the caspase-8 signaling cascade.