Diabetic foot ulcers, affecting millions worldwide, face impaired healing due to dysregulated macrophage polarization. However, the epigenetic mechanisms underlying aberrant macrophage polarization remain to be elucidated. This study introduces a multifunctional, exosome-based delivery platform that combines miR-493-5p-engineered M2 macrophage exosomes with piezoelectric GelMA microneedles to reprogram macrophage metabolism and epigenetics for diabetic wound healing. Engineered EXO@miR-493-5p are embedded in GelMA microneedles (MN) and delivered via a ZnO piezoelectric substrate with a nanosilver/GOx coating to provide antibacterial and antioxidant benefits. Ultrasound-induced electrostimulation enhances exosome deposition and endocytic uptake, enabling sustained, localized cargo release. Mechanistically, miR-493-5p targets HDAC1 to amplify histone H3K18 lactylation, activating the STAT6 axis and driving metabolic reprogramming toward M2 polarization with upregulation of Arg1. In vitro, EXO@miR-493-5p promote M2 markers and angiogenesis. In vivo, they accelerate wound closure, promote re-epithelialization, collagen deposition, and neovascularization, while reducing ROS and inflammation. The integrated platform offers a translatable, epigenetic-metabolic strategy for chronic diabetic wounds.

BACKGROUND AND PURPOSE:Previous studies have highlighted the significance of the bile acid receptor TGR5 (also known as Takeda G protein-coupled receptor 5) in regulating inflammation and mitochondrial homeostasis in various diseases, whereas the specific involvement of TGR5 in spinal cord injury (SCI) remains unclear. This study aimed to elucidate the effects of TGR5 on SCI, as well as the underlying mechanisms. EXPERIMENTAL APPROACH:The TGR5 agonist INT-777 was used to activate TGR5 in a mouse model of SCI, induced by contusion injury to T9-T10 vertebrae, and cultured cells. To determine the mechanism of TGR5 activation after SCI, public dataset analysis, behaviour assessment, histology and biochemical analysis relating to inflammation, pyroptosis and mitochondrial function were performed. KEY RESULTS:TGR5 levels were increased in a mouse model of spinal cord injury (SCI), and in primary microglia and BV2 cells treated with tert-butyl hydroperoxide. Furthermore, TGR5 activation by INT-777 improved functional recovery and tissue repair in SCI mice. Mechanistically, INT-777-mediated TGR5 activation exerted a neuroprotective effect by regulating cAMP/AMPK signalling, resulted in suppression of mitochondrial dysfunction and mitochondrial DNA (mtDNA) release, which inhibited absent in melanoma 2 (AIM2)-driven pyroptosis and the inflammatory response. Notably, AIM2 overexpression partly blocked the neuroprotective effects of TGR5 activation in SCI mice. Additionally, AMPK inhibition by dorsomorphin aggravated neural injury and inflammation was alleviated in AIM2 deletion mice following SCI. CONCLUSIONS AND IMPLICATIONS:INT-777 exerts anti-inflammatory and neuroprotective effects in the injured spinal cord by activating the TGR5/cAMP/AMPK pathway, thereby maintaining mitochondrial homeostasis and suppressing AIM2-mediated pyroptosis.

Oxidative stress-induced dysfunction of nucleus pulposus (NP) cells is a key driver of intervertebral disc degeneration (IDD), promoting accelerated cellular senescence and extracellular matrix (ECM) degradation. Moreover, effective regulation of redox homeostasis within the avascular intervertebral disc remains challenging due to rapid drug clearance and poor targeting. To address these issues, we developed a precision antioxidative therapeutic strategy by integrating edaravone (ED), an FDA-approved free radical scavenger, into a novel reactive oxygen species (ROS)-responsive hydrogel (ED@HFA) for localized intradiscal delivery. Mechanistically, ED restored redox balance and preserved ECM homeostasis in NP cells under oxidative stress by activating the Nrf2/Aldh3a1 signaling axis. From a delivery perspective, ED@HFA employs hyaluronic acid methacrylate (HAMA) as a biomimetic matrix and incorporates 3-fluorophenylboronic acid (FPBA) to construct a redoxsensitive crosslinked network. The electron-withdrawing fluorine substituent in FPBA markedly enhances responsiveness to pathological ROS levels for on-demand drug release. In a puncture-induced rat IDD model, this delivery system effectively preserved disc structural integrity and attenuated IDD progression. Collectively, this precision antioxidative delivery platform, combining the safe and effective antioxidant ED with a novel ROSresponsive hydrogel, provides a promising therapeutic approach for the treatment of IDD.

Intervertebral disc degeneration (IVDD) is a multifactorial process that leads to low back pain. Current managements for IVDD primarily focus on symptomatic relief and do not fundamentally address IVDD, and effective pharmacological interventions for IVDD are still lacking. Ferroptosis has been reported to involve in the pathogenesis and serve as an effective target for IVDD. In the current study, we evaluate the effect of Ethyl gallate (EG) on ferroptosis and its therapeutic potential in IVDD. It was found that EG may effectively suppress ferroptosis in nucleus pulposus cells. Network pharmacology and molecular docking analysis demonstrated that ethyl gallate may activate the AKT1 signaling pathway, which subsequently increase the expression of the ferroptosis suppressor gene GPX4, and reduce the degradation of the extracellular matrix (ECM) and suppress the senescence of nucleus pulposus cells (NPCs). In the rat puncture induced IVDD model, intraperitoneal injection of ethyl gallate delayed the progression of IVDD. In summary, our study indicates that ethyl gallate alleviated IVDD by inhibiting NPCs ferroptosis via activation of AKT1, as well as suppressing the cell senescence and ECM degradation, thus suggesting ethyl gallate as a promising therapeutic drug for IVDD.

The objective of this study was to evaluate risk factors and clinical outcomes in patients with reduction loss after acromioclavicular joint dislocation treated with the Endobutton device and to develop a nomogram prediction model. We conducted a retrospective examination of the medical records of 250 patients who had undergone ligament reconstruction using the Endobutton device. Univariate and multivariate logistic regression analyses were utilized to identify the risk factors. Subsequently, a nomogram model was constructed to forecast the probability of reduction loss. The model’s discrimination and calibration were assessed using a calibration plot, receiver operating characteristic, and decision plot. To evaluate the clinical outcomes of patients experiencing reduction loss, both the Visual Analogue Scale (VAS) score and Constant score were assessed both preoperatively and at the final follow-up. Reduction loss occurred in 25.6

Intervertebral disc degeneration (IVDD) is the main cause of low back pain, pyroptosis is a major contributor to various diseases, including IVDD; however, there is currently no effective drugs targeting pyroptosis for therapy. In this study, we established pyroptosis model in nucleus pulposus cells (NPCs) in vitro and searched pyroptosis inhibitors in FDA Medicine Library. High throughput screening study revealed that Pirfenidone (PFD) was the most effective pyroptosis inhibitor among 1500+ FDA drugs, which was confirmed by further experiments. As administering PFD alone may lead to poor efficacy due to short action time and low bioavailability, we designed a smart delivery system for PFD. A pH-responsive metal-organic framework (MOF), poly-His6-zinc (PHZ) assembly, loaded with PFD (PFD@PHZ) was designed for IVDD therapy. PHZ was shown to have excellent lysosomal escape properties and bioavailability of PFD. In addition, the release of PDF from PFD@PHZ could be triggered by the acidic microenvironment of degenerated intervertebral discs. PFD@PHZ was also shown to effectively inhibit pyroptosis, senescence, and extracellular matrix (ECM) degradation in NPCs, both in vitro and in vivo, thereby mitigating the progression of IVDD in rats. Thus, the current study shows PFD as a novel inhibitor for pyroptosis, and PFD@PHZ as a potential nanomaterial for efficient IVDD therapy.

Mitochondrial oxidative stress and the absent in melanoma 2 (AIM2) inflammasome play crucial roles in the regulation of secondary injury in patients with spinal cord injury (SCI). AIM2 responds to oxidative stress-mediated DNA damage, and this response leads to neuroinflammation. Salt-inducible kinase 2 (SIK2) is an AMPK-related protein kinase that plays a role in modulating cell metabolism and homeostasis. SIK2 and AIM2 are key molecules involved in metabolic regulation and the innate immune response, respectively. There is a potential association between SIK2 and AIM2 in terms of the cellular stress response, DNA damage repair and inflammatory signal transduction. However, the detailed role and mechanisms remain to be fully elucidated in the context of SCI. The present study revealed that SIK2 and AIM2 increase the number of microglia after SCI. Moreover, pharmacological inhibition of SIK2 or genetic deletion of AIM2 improves functional recovery. In addition, the SIK2 inhibitor ARN-3236, which alleviates the neuroinflammatory response, attenuates mitochondrial dysfunction and represses AIM2 activation in microglia. Mechanistically, SIK2 inhibition reduces Drp1-dependent mitochondrial fission through the CRTC1/CREB pathway, thereby decreasing mitochondrial DNA (mtDNA) leakage and AIM2 inflammasome activation, which inhibits the release of pyroptosis-related proteins and proinflammatory cytokines, ultimately mitigating neuroinflammation after SCI. Furthermore, SIK2-mediated neuroinflammation and functional recovery are related to AIM2. Thus, modulating microglial function through inhibition of SIK2 may be a viable therapeutic strategy for promoting functional recovery after SCI.

Per- and polyfluoroalkyl substances (PFAS) have been extensively used in everyday products; however, their effects on human health remain largely unknown. This study aimed to investigate the potential mechanisms by which PFAS may contribute to functional disorders in the human musculoskeletal system. Four representative musculoskeletal disorders were selected, which included intervertebral disc degeneration, myositis, osteoarthritis, and osteoporosis. Advanced network toxicology approaches integrating data from the Comparative Toxicogenomics Database (CTD) and GeneCards identified potential PFAS-associated targets for each disorder. Molecular docking simulations were employed to assess interactions between PFAS and target proteins. Molecular docking of a series of PFAS molecules against multiple protein targets revealed strong binding affinities. Prioritization based on average binding energies highlighted the targets with the greatest PFAS-binding potential. A subsequent comprehensive analysis further discussed these findings by integrating the functional roles of the targets and the classification of the various PFAS compounds. Evidence synthesis confirmed that these core targets are critically involved in key pathological processes common to musculoskeletal diseases, including chronic inflammation, oxidative stress, apoptosis, extracellular matrix degradation, and impaired bone remodeling. This study provides innovative insights into the mechanisms by which environmental pollutants contribute to human diseases, thereby establishing a theoretical foundation for disease prevention and therapeutic strategies.

AIMS:Intervertebral disc degeneration (IVDD) is a leading contributor to spinal degenerative diseases; however, its pathogenesis remains only partially elucidated. Recent studies have highlighted that the diminished activity of SIRT1 and the aberrant activation of the NF-κB signaling pathway are critical pathogenic factors in IVDD. DBC1 has been identified as a regulator of SIRT1 activity and the NF-κB signaling pathway. This study aimed to investigate the role of DBC1 in IVDD. MATERIALS AND METHODS:The expression levels of DBC1 in the nucleus pulposus of aging rats were quantified. Both overexpression and knockdown of DBC1 were utilized to explore their effects on the extracellular matrix (ECM) of the nucleus pulposus. Furthermore, the influence of DBC1 on cellular senescence, apoptosis, and ECM regulation in nucleus pulposus cells was assessed using Western blot (WB), cellular fluorescence assays, and histological staining techniques. KEY FINDINGS:Our results demonstrate that DBC1 expression is significantly upregulated in IVDD. Moreover, DBC1 appears to contribute to IVDD by promoting apoptosis, senescence, and ECM degradation in nucleus pulposus cells. Mechanistic investigations revealed that DBC1 activates the NF-κB signaling pathway while suppressing SIRT1 expression in nucleus pulposus cells, suggesting that these two mechanisms underlie its effects on IVDD. SIGNIFICANCE:In summary, this study provides evidence that DBC1 may play a pivotal role in the pathogenesis of IVDD by inhibiting SIRT1 activity and activating the NF-κB signaling pathway. Consequently, targeting DBC1 suppression could represent a promising therapeutic strategy for managing IVDD.

Study Design. Cross-sectional and retrospective cohort study. Objective. We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. Summary of Background Data. In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. Patients and Methods. A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. Results. Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs. 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). Conclusions. More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. Level of Evidence: Level III. (C) 2023 Wolters Kluwer Health, Inc. All rights reserved.

Osteoarthritis (OA) is the predominant cause of disability among elderly people worldwide and is characterized by cartilage degeneration and excessive bone formation. Phillyrin, derived from forsythia, is a key extract renowned for its pronounced antibacterial and anti-inflammatory effects. Forsythia, deeply integrated into traditional Oriental medicine, has historically been utilized for its various pharmacological effects, including antibacterial, anti-inflammatory, and hepato-protective properties. Nevertheless, the anti-inflammatory impact of phillyrin on the progression of osteoarthritis remains enigmatic. The objective of this research was to assess the anti-inflammatory and anti-aging properties of phillyrin in mouse chondrocytes induced by IL-1β, as well as to elucidate the fundamental mechanisms underlying the phenomenon at play. Additionally, the investigation extends to observing the impact of phillyrin by establishing a murine osteoarthritic model. The ultimate goal was to identify phillyrin as a potential antiosteoarthritic agent. This investigation employs a multifaceted approach. Initially, key action targets of phillyrin, along with its probable action pathways, were identified by molecular docking and network pharmacological techniques. These findings were subsequently confirmed through both in vivo and in vitro studies. Network pharmacological analysis revealed NFE2L2 (NRF2), NFKB1, TLR4, and SERPING1 as pivotal candidate targets for the treatment of osteoarthritis with phillyrin. Molecular docking revealed hydrogen bond interactions between phillyrin and Arg415, Arg483, Ser508, and Asn387 on the Nrf2 receptor, while electrostatic interactions occurred with residues Arg415 and Arg380. Experiments conducted in vitro indicated that phillyrin preconditioning hindered the IL-1β-induced expression of proinflammatory factors which included TNF-α, COX-2, IL-6, and iNOS. Furthermore, phillyrin counteracts the IL-1β-induced degradation of aggrecan and collagen II within the extracellular matrix (ECM). This protective action is caused by the inhibition of the NF-κB pathway by phillyrin. Additionally, the mitigation of chondrocyte aging by phillyrin was observed. Our investigation revealed that phillyrin mitigates inflammation and counteracts cartilage degeneration in osteoarthritis (OA) patients by suppressing inflammation in chondrocytes and impeding aging through suppression of the NF-κB pathway.

BACKGROUND:Erastin has been found to induce ferroptosis; however, whether erastin may have roles other than ferroptosis inducer in cells is unknown. Nutrient deficiency is one of the major causes of many diseases including intervertebral disc (IVD) degeneration. PURPOSE:The current study investigates the effect of erastin in nucleus pulposus cells under nutrient deprivation condition. STUDY DESIGN:Experiment in vitro and ex vivo. METHODS:The effect of erastin on the cell survival of nucleus pulposus cells was evaluated in fetal bovine serum (FBS) and glucose deprivation condition. RSL3 and ferrostatin-1 were applied to illustrate whether the effect of erastin is ferroptosis dependent. The involvement of solute carrier family 7, membrane 11(SLC7A11), autophagy as well as mechanistic target of rapamycin kinase complex 1(mTORC1) and transcription factor EB (TFEB) were assessed to demonstrate the working mechanism of erastin. RESULTS:Erastin may induce cell death at the concentration of ≥ 5μM; however, it may protect nucleus pulposus cells against nutrient deprivation induced cell death at lower concentration (0.25-1μM) and the effect of erastin is ferroptosis independent. The mechanism study showed that the effect of erastin may relate to its SCL7A11 regulation, as SCL7A11 knock-down may have the similar effect as erastin. Furthermore, it was also demonstrated that mTORC1-TFEB mediated autophagy was involved in protective effect of erastin. CONCLUSIONS:Low dose erastin may promote cell survival under nutrient deprivation condition, and its effect is ferroptosis independent; erastin may exert its protective effect through mTORC1-TFEB mediated autophagy regulation. CLINICAL SIGNIFICANCE:Nutrient deprivation is a major contributor to intervertebral disc degeneration. Our in vitro and ex vivo study showed that low dose of erastin may suppress nutrient deprivation induced cell death in IVD degeneration. Although it was not validated in vivo model due to lack of in vivo nutrient deprivation induced IVD degeneration model currently, this study may still provide a potential therapeutic option for IVD degeneration, which of cause need further validation.

Intervertebral disc degeneration (IVDD), a common degenerative disc disease, is a major etiological factor for back pain, affecting a significant number of middle-aged and elderly individuals worldwide. Thus, IVDD is a major socio-economic burden. The factors contributing to the complex IVDD etiology, which has not been elucidated, include inflammation, oxidative stress, and natural aging. In particular, inflammation and aging of nucleus pulposus cells are considered primary pathogenic factors. Isorhapontigenin (ISO) is a polyphenolic compound commonly found in traditional Chinese herbs and grapes. We have demonstrated that ISO exerts anti-inflammatory and anti-aging effects and mitigates extracellular matrix (ECM) degradation. In this study, in vitro experiments revealed that, ISO delays aging and ECM degradation by promoting PI3K/AKT/mTOR-mediated autophagy. Meanwhile, in vivo experiments affirmed that ISO delays the progression of IVDD.

Ethnopharmacological relevance Osteoarthritis (OA) is a degenerative disease, its characteristic lies in the inflammation and extracellular matrix (ECM) degradation, can lead to significant personal disability and social burden. Lycopodium japonicum Thunb. (LJT) is a lycopinaceae plant with anti-inflammatory and analgesic effects. In traditional Oriental medicine, LJT is commonly used to treat a variety of conditions, including osteoarthritis and low back pain. Aim of the study To investigate the anti-apoptotic, anti-inflammatory and anti-senescence properties of LJT in IL-1β-induced mouse chondrocytes, and to clarify the underlying mechanisms involved. In addition, the study also examined the effects of LJT by establishing a mouse model of osteoarthritis. The ultimate goal is to identify the mechanism of LJT as an anti-osteoarthritis agent. Materials and methods In this research, molecular docking and network pharmacology analysis were performed to identify the latent pathways and key targets of LJT action. The CCK-8 kit was used to evaluate LJT's effect on chondrocyte viability. Western blotting, Immunofluorescence, TUNEL staining kit, and SA-β-gal staining were employed to verify LJT's impact on chondrocytes. Additionally, SO, HE, and Immunohistochemical were utilized to assess LJT's effects on osteoarthritis in mice. In vitro and in vivo experiments were performed to verify the potential mechanism of LJT in OA. Results Network pharmacology analysis revealed that AKT1, PTGS2, and ESR1 were the key candidate targets for the treatment of OA with LJT. The results of molecular docking indicated that AKT1 exhibited a low binding affinity to the principal constituents of LJT. Hence, we have chosen STING, an upstream regulator of PTGS2, as our target for investigation. Molecular docking revealed that sitosterol, formononetin, stigmasterol and alpha-Onocerin, the main components of LJT, have good binding activity with STING. In vitro experiments showed that LJT inhibited IL-1β-mediated secretion of inflammatory mediators, apoptosis and senescence of chondrocytes. The results showed that LJT abolished cartilage degeneration induced by unstable medial meniscus (DMM) in mice. Mechanism research has shown that LJT by inhibiting the STING/NF-κB signaling pathways, down-regulating the NF-κB activation, so as to inhibit the development of OA. Conclusion LJT reversed the progression of OA by inhibiting inflammation, apoptosis and senescence in animal models and chondrocytes. The effects of LJT are mediated through the STING/NF-κB pathway.

Study Design. Cross-sectional and retrospective cohort study. Objective. We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. Summary of Background Data. In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. Patients and Methods. A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. Results. Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs. 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). Conclusions. More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. Level of Evidence: Level III.

Osteoarthritis (OA), which is a major cause of serious arthralgia and disability among the elderly, has long plagued numerous populations. However, the specific molecular mechanisms involved in the etiology of OA are unclear. SIRT6 plays a critical function in the development of several inflammatory and aging-associated diseases. A study by D'Onofrio demonstrates that ergothioneine (EGT) is an effective activator of SIRT6. As revealed by previous reports, EGT exerts beneficial effects on the mouse body, including resistance to oxidation, tumor, and inflammation. Therefore, this work attempted to identify the inflammatory resistance of EGT and explore its effects on the incidence and development of OA. Mouse chondrocyte stimulation using varying levels of EGT and 10 ng/mL IL-1β. According to in vitro experiments, EGT significantly reduced the decomposition of collagen II and aggrecan in OA chondrocytes, as well as inhibited the overexpression of PGE2, NO, IL-6, TNF-α, iNOs, COX-2, MMP-13, and ADAMTS5. In the present work, EGT hindered the NF-κB activity by activating the SIRT6 pathway in OA chondrocytes, which in turn, significantly attenuated the inflammatory response resulting from IL to 1β. The inhibitory effect of EGT on the progression of OA was demonstrated by the mouse DMM model experiment. Thus, this study revealed that EGT was effective in anti-OA treatment.