scholarly journals Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis

2020 ◽  
Vol 21 (4) ◽  
pp. 1541 ◽  
Author(s):  
Yeon-Hee Lee ◽  
Hee-Kyung Park ◽  
Q-Schick Auh ◽  
Haram Nah ◽  
Jae Seo Lee ◽  
...  

Exosomes are nanosized vesicles (30–140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration.

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Dixin Cui ◽  
Hongyu Li ◽  
Xin Xu ◽  
Ling Ye ◽  
Xuedong Zhou ◽  
...  

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Jian Yuan ◽  
Wanghui Ding ◽  
Na Wu ◽  
Shijie Jiang ◽  
Wen Li

Temporomandibular joint osteoarthrosis (TMJOA) is characterised by chronic inflammatory changes, with subsequent gradual loss of joint cartilage. NF-κB is a crucial transcription factor in the course of inflammatory and immune responses, which are involved in OA pathology activated by proinflammatory cytokines. Genistein is known to have anti-inflammation and modulation of metabolic pathways through repression of the NF-κB signaling pathway in inflammatory disease. But so far, studies on the effects of genistein on TMJOA are very limited. So, the purpose of this study is to investigate the protective effect of genistein against experimentally induced condylar cartilage degradation through downregulating NF-κB expression in created osteoarthritis rats in vivo. Male SD rats were created as temporomandibular joint osteoarthritis models and administered through oral gavage with low and high dosage genistein (30 mg/kg and 180 mg/kg, respectively) daily for 4 weeks. The morphological changes of the condylar cartilage were studied with HE and Masson staining. The expressions of p65 and inflammatory cytokines (IL-1β and TNFα) were detected using immunohistochemistry and real-time PCR. The results showed that experimentally created osteoarthritis reduced the condylar cartilage thickness of rats and increased the gene expression of cytokines (IL-1β and TNFα) and positive cells of p65. Genistein treatment had positive effects on the condylar cartilage renovation, while high dose genistein treatment had more significant effects on the reversing of OA changes and reduction of the expression of p65 and inflammatory cytokines (IL-1β and TNFα). The results indicated that high dose genistein treatment had obvious therapeutic effects on condyle cartilage damages of OA rats. The mechanism may be that genistein suppresses the NF-κB expression activated by inflammatory cytokines.


2020 ◽  
Author(s):  
Mengying Jia ◽  
Yaoguang Lv ◽  
Yingjie Xu ◽  
Zhoncheng Gong

Abstract Background: Pyroptosis is the highlight topic in inflammation. However, there is rarely research on relationship between pyroptosis and temporomandibular joint osteoarthritis (TMJOA), The aim of this study is to explore whether pyroptosis related molecules are significant for condylar cartilage degeneration and to verify the clinical effects of sodium hyaluronic acid (HA) treatment on TMJOA.Methods: Patients diagnosed as temporomandibular joint internal derangement (TMJID) without condylar defect and TMJOA with condylar defect were divided into two groups. Thirty patients in each group, and they were tested for pyroptosis related molecules via synovial fluid included interleukin-1beta (IL-1β), IL-18, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (CASP1) with Enzyme-linked immunosorbent assay(Elisa). Eighteen cases in TMJOA group were tested again after twice HA treatment to evaluate HA’s therapeutic effects. Results: IL-1β, IL-18, NLRP3 and CASP1 were all positive in two groups, TMJOA patients with condylar defect had higher expressions of above molecules compared with TMJID patients (P<0.05). IL-1β, IL-18, NLRP3 were decreased with twice HA therapy (P<0.05), there was no significant difference in CASP1 with twice HA injections (P=0.549). Conclusions: Cell pyroptosis may be involved in condylar degeneration. HA could reduce part of pyroptosis molecules to relieve inflammation.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mengying Jia ◽  
Yaoguang Lv ◽  
Yingjie Xu ◽  
Zhongcheng Gong

Abstract Background The nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathway is a highlighted topic in the field of inflammation. However, there is little research on the relationship between the NLRP3 inflammasome pathway and temporomandibular joint osteoarthritis (TMJOA). The aim of this study was to examine the expression of inflammatory mediators related to the NLRP3 inflammasome in the synovial fluid of patients with condylar cartilage degeneration and verify the clinical effects of sodium hyaluronic acid (HA) treatment on TMJOA. Methods Patients diagnosed with temporomandibular joint internal derangement (TMJID) without condylar defects and TMJOA with condylar defects were divided into two groups. There were thirty patients in each group, and inflammatory mediators related to the NLRP3 inflammasome, including interleukin-1 beta (IL-1β), IL-18, NLRP3, and cysteinyl aspartate specific proteinase 1 (CASP1), in synovial fluid were measured by enzyme-linked immunosorbent assay (ELISA). Eighteen patients in the TMJOA group were retested after two HA treatments to evaluate the therapeutic effects of HA. Results IL-1β, IL-18, NLRP3 and CASP1 were all positive in the two groups, and TMJOA patients with condylar defects had higher expression of these molecules than TMJID patients (P < 0.05). IL-1β, IL-18, and NLRP3 were decreased after two HA treatments (P<0.05), but there was no significant difference in CASP1 after two HA injections (P = 0.549). Conclusions The NLRP3 inflammasome signaling pathway may be involved in condylar degeneration. HA could reduce some inflammatory molecules to alleviate inflammation.


2022 ◽  
Author(s):  
Jun Zhang ◽  
Yu Hu ◽  
Zihan Wang ◽  
Xuelian Wu ◽  
Chun Yang ◽  
...  

Abstract Background: It remains unclear whether hypoxic conditions affect apoptosis and contribute to degradation of cartilaginous tissues in osteoarthritis (OA) lesions. In this study, we hypothesized that hypoxic conditions induced the accumulation of hypoxia-inducible factor (HIF) and activated apoptosis to contribute to OA cartilage degeneration in vivo.Methods: Malocclusion stress was applied for 2 weeks, 4 weeks and 8 weeks to induce an OA-like lesion animal model (OD) in rats. Histological analysis was performed by H&E staining and safranin O/fast green staining. The expression levels of protein in condylar cartilage were examined by immunostaining to evaluate cartilage degeneration.Results: We found apparent histological phenotypes associated with degeneration in the occlusion disorder stress (OD) group. The OD group at 4 weeks and 8 weeks had obviously reduced expression of Acan and Col II in cartilage. In contrast, the OD groups had higher levels of Col X, ADAMTS5 and MMP13 in the condylar cartilage than the control group. Moreover, the OD group cartilage had prominent degenerative changes with reduced levels of HIF1α and increased levels of HIF2α and the apoptosis factor Caspase3 in condylar cartilage at 8 weeks.Occlusion disorder stress results in cartilage degeneration. HIF1α and HIF2α are involved in temporomandibular joint (TMJ) cartilage homeostasis by regulating chondrocyte apoptosis, which contributes to TMJ cartilage degeneration. Conclusion: Thus, abnormal hypoxic conditions inducing opposite expression patterns of HIF1α and HIF2α could be involved in the pathogenesis of condylar cartilage degeneration. HIF2α may provide a potential negative feedback mechanism for HIF1α during cartilage damage.


2020 ◽  
Vol 23 (4) ◽  
pp. 11p
Author(s):  
Abdelrahman Mohamed Galal Abdelhameed ◽  
Said Mahmoud Mohamed Hani ◽  
Ahmed Mohamed Mohamed Soliman

Objectives: morin hydrate has been reported to possess many beneficial pharmacological potentialities including antioxidant and anti-osteoarthritic effects. The antiosteoarthritic properties of locally administrated morin have not been investigated. The objective of this study is to evaluate the locally delivered morin on the temporomandibular joint osteoarthritis in rat.  Materials and methods: thirty young adult female Sprague Dawley rats were randomly arranged into three groups; control, osteoarthritis and osteoarthritis with morin. Both the iodoacetate for osteoarthritis induction and morin hydrate therapy were delivered unilaterally via intra-articular route. Results: morin reduced osteoarthritis manifestations with prominent thickening of both condylar fibrous layer and articular disc accompanied with discal cells hypertrophy that ultimately acquired chondrocytes features. The condylar cartilage matrix showed enhancement of extracellular matrix production with morin administration. Discussion: the present study has elucidated antiosteoarthritic effect of intraarticular injection of morin hydrate. Although morin has managed to prevent the propagation and advancing some of the recorded osteoarthritic manifestations; however, it showed some failure in managing others. The administration of morin hydrate modulated the structure of the joint rather than restore it back to its typical configuration. Conclusion: the morin hydrate administration to osteoarthritic animals showed relieve in some of osteoarthritic features and modulated the structure of some joint components to compensate the unhandled manifestations.KEYWORDSIodoacetate; Morin; Osteoarthritis; OARSI Score;  Temporomandibular joint.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yifan Zhao ◽  
Liang Xie

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by cartilage degeneration, disrupted subchondral bone remodeling, and synovitis, seriously affecting the quality of life of patients with chronic pain and functional disabilities. Current treatments for TMJOA are mainly symptomatic therapies without reliable long-term efficacy, due to the limited self-renewal capability of the condyle and the poorly elucidated pathogenesis of TMJOA. Recently, there has been increased interest in cellular therapies for osteoarthritis and TMJ regeneration. Mesenchymal stem cells (MSCs), self-renewing and multipotent progenitor cells, play a promising role in TMJOA treatment. Derived from a variety of tissues, MSCs exert therapeutic effects through diverse mechanisms, including chondrogenic differentiation; fibrocartilage regeneration; and trophic, immunomodulatory, and anti-inflammatory effects. Here, we provide an overview of the therapeutic roles of various tissue-specific MSCs in osteoarthritic TMJ or TMJ regenerative tissue engineering, with an additional focus on joint-resident stem cells and other cellular therapies, such as exosomes and adipose-derived stromal vascular fraction (SVF). Additionally, we summarized the updated pathogenesis of TMJOA to provide a better understanding of the pathological mechanisms of cellular therapies. Although limitations exist, MSC-centered therapies still provide novel, innovative approaches for TMJOA treatment.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qingyuan Zheng ◽  
Shuijun Zhang ◽  
Wen-Zhi Guo ◽  
Xiao-Kang Li

Methods for suppressing the host immune system over the long term and improving transplantation tolerance remain a primary issue in organ transplantation. Cell therapy is an emerging therapeutic strategy for immunomodulation after transplantation. Mesenchymal stem cells (MSCs) are adult multipotent stem cells with wide differentiation potential and immunosuppressive properties, which are mostly used in regenerative medicine and immunomodulation. In addition, emerging research suggests that MSC-derived exosomes have the same therapeutic effects as MSCs in many diseases, while avoiding many of the risks associated with cell transplantation. Their unique immunomodulatory properties are particularly important in the immune system-overactive graft environment. In this paper, we review the effects of MSC-derived exosomes in the immune regulation mechanism after organ transplantation and graft-versus-host disease (GvHD) from various perspectives, including immunosuppression, influencing factors, anti-inflammatory properties, mediation of tissue repair and regeneration, and the induction of immune tolerance. At present, the great potential of MSC-derived exosomes in immunotherapy has attracted a great deal of attention. Furthermore, we discuss the latest insights on MSC-derived exosomes in organ transplantation and GvHD, especially its commercial production concepts, which aim to provide new strategies for improving the prognosis of organ transplantation patients.


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