Cartilage Breakdown Research Articles

Post-traumatic knee osteoarthritis; the role of inflammation and hemarthrosis on disease progression.

Knee injuries such as anterior cruciate ligament ruptures and meniscal injury are common and are most frequently sustained by young and active individuals. Knee injuries will lead to post-traumatic osteoarthritis (PTOA) in 25–50% of patients. Mechanical processes where historically believed to cause cartilage breakdown in PTOA patients. But there is increasing evidence suggesting a key role for inflammation in PTOA development. Inflammation in PTOA might be aggravated by hemarthrosis which frequently occurs in injured knees. Whereas mechanical symptoms (joint instability and locking of the knee) can be successfully treated by surgery, there still is an unmet need for anti-inflammatory therapies that prevent PTOA progression. In order to develop anti-inflammatory therapies for PTOA, more knowledge about the exact pathophysiological mechanisms and exact course of post-traumatic inflammation is needed to determine possible targets and timing of future therapies.

Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression

The accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related diseases such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin 43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage. OA has been reclassified as a musculoskeletal disease characterized by the breakdown of the articular cartilage affecting the whole joint, subchondral bone, synovium, ligaments, tendons and muscles. However, the mechanisms that contribute to the spread of pathogenic factors throughout the joint tissues are still unknown. Here, we show for the first time that small extracellular vesicles (sEVs) released by human OA-derived chondrocytes contain high levels of Cx43 and induce a senescent phenotype in targeted chondrocytes, synovial and bone cells contributing to the formation of an inflammatory and degenerative joint environment by the secretion of senescence-associated secretory associated phenotype (SASP) molecules, including IL-1ß and IL-6 and MMPs. The enrichment of Cx43 changes the protein profile and activity of the secreted sEVs. Our results indicate a dual role for sEVs containing Cx43 inducing senescence and activating cellular plasticity in target cells mediated by NF-kß and the extracellular signal-regulated kinase 1/2 (ERK1/2), inducing epithelial-to-mesenchymal transition (EMT) signalling programme and contributing to the loss of the fully differentiated phenotype. Our results demonstrated that Cx43-sEVs released by OA-derived chondrocytes spread senescence, inflammation and reprogramming factors involved in wound healing failure to neighbouring tissues, contributing to the progression of the disease among cartilage, synovium, and bone and probably from one joint to another. These results highlight the importance for future studies to consider sEVs positive for Cx43 as a new biomarker of disease progression and new target to treat OA.

Coenzyme Q10 encapsulated in micelles ameliorates osteoarthritis by inhibiting inflammatory cell death.

Osteoarthritis (OA) is the most common degenerative joint disease and is characterized by breakdown of joint cartilage. Coenzyme Q10 (CoQ10) exerts diverse biological effects on bone and cartilage; observational studies have suggested that CoQ10 may slow OA progression and inflammation. However, any effect of CoQ10 on OA remains unclear. Here, we investigated the therapeutic utility of CoQ10-micelles. Seven-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. CoQ10-micelles were administered orally to MIA-induced OA rats; celecoxib served as the positive control. Pain, tissue destruction, and inflammation were measured. The expression levels of catabolic and inflammatory cell death markers were assayed in CoQ10-micelle-treated chondrocytes. Oral supplementation with CoQ10-micelles attenuated OA symptoms remarkably, including pain, tissue destruction, and inflammation. The expression levels of the inflammatory cytokines IL-1β, IL-6, and MMP-13, and of the inflammatory cell death markers RIP1, RIP3, and pMLKL in synovial tissues were significantly reduced by CoQ10-micelle supplementation, suggesting that CoQ10-micelles might attenuate the synovitis of OA. CoQ10-micelle addition to cultured OA chondrocytes reduced the expression levels of catabolic and inflammatory cell death markers. CoQ10-micelles might usefully treat OA.

Icariin: A Potential Molecule for Treatment of Knee Osteoarthritis.

Background: Knee osteoarthritis (KOA) is a degenerative disease that develops over time. Icariin (ICA) has a positive effect on KOA, although the mechanism is unknown. To investigate drug-disease connections and processes, network pharmacology is commonly used. The molecular mechanisms of ICA for the treatment of KOA were investigated using network pharmacology, molecular docking and literature research approaches in this study. Methods: We gathered KOA-related genes using the DisGeNET database, the OMIM database, and GEO microarray data. TCMSP database, Pubchem database, TTD database, SwissTargetPrediction database, and Pharmmapper database were used to gather ICA-related data. Following that, a protein-protein interaction (PPI) network was created. Using the Metascape database, we performed GO and KEGG enrichment analyses. After that, we built a targets-pathways network. Furthermore, molecular docking confirms the prediction. Finally, we looked back over the last 5 years of literature on icariin for knee osteoarthritis to see if the findings of this study were accurate. Results: core targets relevant to KOA treatment include TNF, IGF1, MMP9, PTGS2, ESR1, MMP2 and so on. The main biological process involved regulation of inflammatory response, collagen catabolic process, extracellular matrix disassembly and so on. The most likely pathways involved were the IL-17 signaling pathway, TNF signaling pathway, Estrogen signaling pathway. Conclusion: ICA may alleviate KOA by inhibiting inflammation, cartilage breakdown and extracellular matrix degradation. Our study reveals the molecular mechanism of ICA for the treatment of KOA, demonstrating its potential value for further research and as a new drug.

Stem cell-homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model.

Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose a hydrogel-based miRNA delivery strategy to rejuvenate impaired cartilage by creating a regenerative microenvironment to mitigate chondrocyte senescence that mainly contributes to cartilage breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found to be markedly down-regulated in OA cartilage, and their up-regulation suppressed the expression of matrix metalloproteinases and senescence-associated genes (P16INK4a/P21) via ten-eleven-translocation enzyme 1 (TET1). An injectable bioactive self-assembling peptide nanofiber hydrogel was applied to deliver agomir-29b-5p, which was functionalized by conjugating a stem cell–homing peptide SKPPGTSS for endogenous synovial stem cell recruitment simultaneously. Sustained miR-29b-5p delivery and recruitment of synovial stem cells and their subsequent differentiation into chondrocytes led to successful cartilage repair and chondrocyte rejuvenation. This strategy enables miRNA-based therapeutic modality to become a viable alternative for surgery in OA treatment.

Quantifying Asymmetry Between Medial and Lateral Compartment Knee Loading Forces Using Acoustic Emissions.

Osteoarthritis is the most common type of knee arthritis that can be affected by excessive and compressive loads and can affect one or more compartments of the knee: medial, lateral, and patellofemoral. The medial compartment tends to be the most vulnerable to injuries and research suggests that a better understanding of the medial to lateral load distribution conditions could provide insights to the quantitative usage of knee compartments in activities of daily life. Prior to study in an osteoarthritic clinical population which may present with various complicating anatomical and physiological changes, we investigate knee acoustical emissions of able-bodied individuals during a varying width squat exercise which simulates loading asymmetries that would typically be seen in this clinical population. To that end, we present a novel method to quantify the directional bias of asymmetry between the medial and lateral compartment knee joint load in healthy individuals by recording knee acoustical emissions and analyzing them using a deep neural network in a subject independent model. We placed four miniature contact microphones on the medial and lateral sides of the patella on both the left and right leg. We compared the handcrafted audio features with the automated features extracted from the convolutional autoencoder which is an unsupervised model that learns the comprehensive representation of the input to determine whether these automated features can better represent the signal's characteristic in regard to the structural asymmetry of the knee joint. The input to the convolutional auto encoder (CAE) is a time-frequency representation and different types of these images such as spectrogram and scalogram are compared. We alsocompared the multi-sensor fusion approach with the performance of a single sensor to determine the robustness of using multiple sensors. Using a representation learning based approach, we developed a subject independent classification model capable of classifying the asymmetry of the medial and lateral joint load across subjects (accuracy = 83%). The result indicates that wavelet coherence which is the time-frequency correlation of two signals using a wavelet transform yields the best accuracy. These findings suggest that acoustic signals could potentially quantify the direction of medial to lateral load distribution which would broaden the implications for wearable sensing technology for monitoring cartilage health and factors responsible for cartilage breakdown and assessing appropriate rehabilitation exercises without overloading on one side.

CHARACTERISATION OF SENESCENCE MARKERS IN VIVO IN AN AGE-RELATED OSTEOARTHRITIS MURINE MODEL AND IN VITRO IN AN IL-1β-INDUCED INFLAMMATORY OSTEOARTHRITIS MODEL AND AN ETOPOSIDE-INDUCED SENESCENCE MODEL

Purpose: Osteoarthritis (OA), the main osteoarticular disease is characterized by cartilage breakdown, synovial inflammation, osteophytes production, and subchondral bone remodeling. While OA is one of the most common rheumatic disorders, no efficient disease-modifying drugs still exist today. Ageing, a complex physiological process, consists of a gradual decline in certain functions, coordination, loss of homeostasis and physiological integrity, is a major risk factor for OA. Like in ageing, an accumulation of senescent cells is observed within the OA joint, and elimination of senescent cells has been shown to reduce pain and increase cartilage development in murine post-traumatic OA.

PROGRESSIVE CARTILAGE BREAKDOWN ASSOCIATED WITH UNDER-LOADING AND LACK OF DYNAMIC CONTROL ONE YEAR AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION

Purpose: After an anterior cruciate ligament (ACL) injury, up to 50% to 80% of patients will develop radiographic evidence of posttraumatic osteoarthritis (PTOA). The injury and reconstructive surgery initiates a complex mechanobiologic disease process with subsequent alterations knee joint biomechanics that is believed to result in joint degeneration. This relationship is poorly understood and the effects of strenuous conditions, such as those experienced during running and landing, on cartilage breakdown are unknown.

BLOCKING ROR2 IMPROVES CARTILAGE INTEGRITY AND PROVIDES PAIN RELIEF IN OSTEOARTHRITIS, IN PART BY MODULATING YAP SIGNALLING

Purpose: Osteoarthritis (OA) is the leading cause of chronic disability worldwide, affecting 12% of the population, and yet we still do not have a disease-modifying treatment. Cartilage breakdown is the hallmark of OA, and patients suffer from pain and loss of joint function/independence, severely affecting quality of life. Therefore, there is a huge unmet clinical need. Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a non-canonical WNT receptor that regulates the planar cell polarity pathway, controlling limb outgrowth during development.

DEFINING THE EFFECTS OF LOAD AND SLIDING SPEED ON THE ABILITY OF CARTILAGE TO SUPPORT LOAD

Purpose: A key feature of osteoarthritis (OA) is the breakdown of articular cartilage. The function of cartilage depends on its ability to support high loads via pressurization of its interstitial fluid—known as “fluid load support” (FLS). FLS depends on the balance of fluid exudation, which occurs during static loading, and fluid rehydration, which occurs during dynamic loading (e.g., walking). Importantly, when exudation and rehydration are perfectly balanced, cartilage achieves dynamic equilibrium deformation (DED).

EXOSOMAL CX43 DRIVES OSTEOARTHRITIS PROGRESSION BY ENHANCING CELLULAR PLASTICITY

Purpose: The accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related pathologies such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage. OA has been reclassified as a musculoskeletal disease characterized by the breakdown of the articular cartilage affecting the whole joint, subchondral bone, synovium, ligaments, tendons and muscles.

SILENCING INFLAMMATORY SIGNALS IN CHONDROCYTES BY CRISPR/CAS9 FOR TISSUE ENGINEERED CELL THERAPY IN OSTEOARTHRITIS

Purpose: Osteoarthritis (OA) is one of the most common degenerative joint diseases, with limited therapeutic options that mostly focus on pain reduction. Restoration of cartilage surface by cell therapies is not effective due to the highly inflamed environment in the osteoarthritic joint. In OA, soluble IL-1β, LPS and TNFα activate the NFKB pathway in chondrocytes, leading to subsequent expression of other pro-inflammatory cytokines and cartilage-degrading enzymes and ultimately degenerative cartilage breakdown.

P13K-AKT PATHWAY AND PERIOSTIN UPREGULATED AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: POTENTIAL ROLE IN EARLY POSTTRAUMATIC CARTILAGE DEGRADATION?

Purpose: Currently the standard of care for anterior cruciate ligament (ACL) injury in the United States is reconstruction, and while surgery has been demonstrated to improve patient-reported outcomes and restore ligamentous stability, ACL reconstruction has not been found to be protective against posttraumatic osteoarthritis (PTOA). Previous studies have demonstrated that ACL injury triggers a series of inflammatory events that leads to a sustained increase in inflammatory cytokines and biomarkers of cartilage breakdown in synovial fluid, and this process is re-initiated after ACL reconstruction.

Changes in ankle and foot kinematic after fixed-bearing total ankle replacement

Ankle osteoarthritis is a chronic debilitating disease marked by cartilage breakdown, pain and significant biomechanical impairment of the entire lower limb. Total ankle replacement (TAR) has been encouraged during the last decade as it has the potential to maintain the existing pre-operative ankle range of motion and to protect the more distally located joints of the foot. Three-dimensional gait analysis using a multi-segment foot model can provide an objective analysis of TAR for the treatment of end-stage ankle osteoarthritis. Thirty-six patients suffering from post-traumatic end-stage ankle osteoarthritis were evaluated before and after TAR. A four-segment kinematic foot model was used to calculate intrinsic foot joint kinematics during gait. Spatio-temporal parameters were also assessed. Kinematic results were compared to a control group of asymptomatic subjects.Differences in waveform patterns were mainly limited to dorsi-/plantarflexion inter-segment angles. At loading response, the Shank-Calcaneus plantarflexion angles as well as the Calcaneus-Midfoot dorsiflexion angle increased slightly in post-operative condition. During propulsion, an increase in Hallux-Metatarsus dorsiflexion angle was observed. Pain improved after surgery as supported by increased spatio-temporal parameters. While multi-segment foot and ankle kinematics were improved, they remained impaired compared to control values. This study confirms that TAR maintains the residual pre-operative range of motion after surgery from midstance to propulsion. Furthermore, the results suggest that the kinematic behavior of the foot joints distal to the affected ankle joint also improves post-operatively. The outcome of this study further emphasizes the clinical relevance of multi-segment foot modeling when assessing the outcome of TAR.

Multibody Computer Model of the Entire Equine Forelimb Simulates Forces Causing Catastrophic Fractures of the Carpus during a Traditional Race.

Simple SummaryPalios are traditional horseraces held in the main square of few Italian cities. Due to peculiar features of such circuits, adapted to the square architecture and thus characterized by tight curves and unconventional footing surface, horses involved are at particular risk of accidents. Prevention of catastrophic musculoskeletal injuries is a significant issue and matter of debate during these events. In particular, the negotiation of the curves in the city circuits is a significative concern. An experiment was set up to build a model of entire forelimb at the point of failure in the context of a turn comparable to that in a Palio circuit. The model was informed by live data and the output compared to post-mortem findings obtained from a horse that sustained a catastrophic fracture of the carpus during this competition. The objective of this study is to determine the magnitude and distribution of internal forces generated across the carpus under which the catastrophic injury has occurred and describe related post-mortem findings.A catastrophic fracture of the radial carpal bone experienced by a racehorse during a Palio race was analyzed. Computational modelling of the carpal joint at the point of failure informed by live data was generated using a multibody code for dynamics simulation. The circuit design in a turn, the speed of the animal and the surface characteristics were considered in the model. A macroscopic examination of the cartilage, micro-CT and histology were performed on the radio-carpal joint of the limb that sustained the fracture. The model predicted the points of contact forces generated at the level of the radio-carpal joint where the fracture occurred. Articular surfaces of the distal radius, together with the proximal articular surface of small carpal bones, exhibited diffuse wear lines, erosions of the articular cartilage and subchondral bone exposure. Even though the data in this study originated from a single fracture and further work will be required to validate this approach, this study highlights the potential correlation between elevated impact forces generated at the level of contact surfaces of the carpal joint during a turn and cartilage breakdown in the absence of pre-existing pathology. Computer modelling resulted in a useful tool to inversely calculate internal forces generated during specific conditions that cannot be reproduced in-vivo because of ethical concerns.

Management of osteoarthritis: From drug molecules to nano/micromedicines.

With the change in lifestyle and aging of the population, osteoarthritis (OA) is emerging as a major medical burden globally. OA is a chronic inflammatory and degenerative disease initially manifesting with joint pain and eventually leading to permanent disability. To date, there are no drugs available for the definitive treatment of osteoarthritis and most therapies have been palliative in nature by alleviating symptoms rather than curing the disease. This coupled with the vague understanding of the early symptoms and methods of diagnosis so that the disease continues as a global problem and calls for concerted research efforts. A cascade of events regulates the onset and progression of osteoarthritis starting with the production of proinflammatory cytokines, including interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α; catabolic enzymes, such as matrix metalloproteinases (MMPs)‐1, ‐3, and ‐13, culminating into cartilage breakdown, loss of lubrication, pain, and inability to load the joint. Although intra‐articular injections of small and macromolecules are often prescribed to alleviate symptoms, low residence times within the synovial cavity severely impair their efficacy. This review will briefly describe the factors dictating the onset and progression of the disease, present the current clinically approved methods for its treatment and diagnosis, and finally elaborate on the main challenges and opportunities for the application of nano/micromedicines in the treatment of osteoarthritis. Thus, future treatment regimens will benefit from simultaneous consideration of the mechanobiological, the inflammatory, and tissue degradation aspects of the disease.This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyImplantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

Sex, but not age and bone mass index positively impact on the development of osteochondral micro-defects and the accompanying cellular alterations during osteoarthritis progression.

BackgroundOsteoarthritis (ΟΑ) is characterized by cartilage breakdown and subchondral sclerosis. Micro‐fractures of the calcified tissues have been, also, detected, but their exact role has not been elucidated yet. This study was to examine the frequency of cracks during OA progression and to correlate them with the underlying cellular modifications and matrix metalloproteinase‐2 (MMP‐2) expression using histological/immunohistological methods.MethodsOverall, 20 patients and 3 controls (9 specimens per patient), aged 60–89 years, diagnosed with hip/knee OA were included. The development of cracks was examined in 138 sections, whereas the expression of MMP‐2 was examined in 69 additional sections.ResultsBased on Mankin score, three groups of OA severity were analyzed: Group I (mild) was constituted of sections with score 1–5 while Groups II (moderate) and III (severe) with score 6–7 and greater or equal to 8, respectively. Demographic characteristics did not reveal any association between the number of microdefects and age or body mass index (BMI). Cartilage micro‐cracks were increased during moderate and severe OA, while bone cracks were increased during mild and severe OA. In knee OA, cartilage cracks were not correlated with Mankin score, whereas in hip OA they appeared association with severity score. Bone cracks were positively correlated with matrix apoptotic osteocytes and osteoblastic cells, but not with osteoclasts. MMP‐2 immunostaining was increasing by OA severity in the osteochondral unit. Similarly, MMP‐2 was expressed on the microcracks’ wall mainly in Group III.ConclusionOur data displayed that bone cracks during primary OA stages, represent an early adaptative mechanism aiming to maintain cartilage integrity. Accumulation of bone defects and concomitant increase of apoptotic osteocytes activated an abnormal remodeling due to osteoblastic activity, in which MMP‐2 played a pivotal role, leading to subchondral sclerosis promoting further osteochondral deformities.

MANAGEMENT OF PHYSIOTHERAPY IN THE CASE OF OSTEOARTHRITIS GENU DEXTRA IN KRAKATAU MEDIKA HOSPITAL

Background: Osteoarthritis is also known as calcification of the joints. The main disorder of osteoarthritis is the breakdown of joint cartilage. Joint cartilage is a joint component that lines the ends of bones in joints, functions as a cushion and shock absorber when two bones collide when the joint is moved (1) Complaints of joint pain usually come and go and attack only a few joints. In
 
 
 the early stages, joint pain occurs after strenuous physical exercise and then disappears after rest. The complaint then progresses to joint stiffness when you wake up in the morning which disappears within 15-30 minutes and decreases after being moved (2). Objective: to determine the management of physiotherapy in the condition of genu dextra osteoarthritis at the Krakatau medika hospital. Method: quantitative research with cross sectional design. Measurement of research variables was only done once by observation. Results: The patient did the examination, there was motion pain in the right knee joint, limited right knee LGS, decreased muscle strength. Parameters used to evaluate pain using a vase, LGS with Goneo Meter, muscle strength with MMT. Patients have difficulty walking long distances, squatting to standing, for toileting, limited range of motion, decreased muscle strength. In this case the management given is MWD, Tens, exercise therapy (isometric exercise, Hold Relax). Conclusion: Giving these three modalities greatly affects the condition of knee osteoarthritis, which can help prevent and treat problems such as:1. reduce pain in the knee starting from tenderness and movement using the VDS scale, 2. increasing the range of motion of the joint with a goneometer, 3. increasing muscle strength with MMT, 4. increasing the patient's functional activity with the jette scale. Suggestion: Physiotherapists are advised to always try to improve knowledge so as to identify problems that can arise in patients and can perform appropriate physiotherapy interventions for successful therapy.

Liraglutide, a glucagon-like peptide 1 receptor agonist, exerts\xa0analgesic, anti-inflammatory and anti-degradative actions in osteoarthritis

Osteoarthritis (OA) is a common disabling disease worldwide, with no effective and safe disease-modifying drugs (DMOAD) in the market. However, studies suggest that drugs, such as liraglutide, which possess strong potential in decreasing low-grade systemic inflammation may be effective in treating OA. Therefore, the aim of this study was to examine the anti-inflammatory, analgesic, and anti-degradative effects in OA using in vitro and in vivo experiments. The results showed that intra-articular injection of liraglutide alleviated pain-related behavior in in vivo sodium monoiodoacetate OA mouse model, which was probably driven by the GLP-1R-mediated anti-inflammatory activity of liraglutide. Moreover, liraglutide treatment significantly decreased IL-6, PGE2 and nitric oxide secretion, and the expression of inflammatory genes in vitro in chondrocytes and macrophages in a dose-dependent manner. Additionally, liraglutide shifted polarized macrophage phenotype in vitro from the pro-inflammatory M1 phenotype to the M2 anti-inflammatory phenotype. Furthermore, liraglutide exerted anti-catabolic activity by significantly decreasing the activities of metalloproteinases and aggrecanases, a family of catabolic enzymes involved in cartilage breakdown in vitro. Overall, the findings of this study showed that liraglutide ameliorated OA-associated pain, possess anti-inflammatory and analgesic properties, and could constitute a novel therapeutic candidate for OA treatment.

Mitochondrial Transplantation Ameliorates the Development and Progression of Osteoarthritis.

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.