TFAM-mediated intercellular lipid droplet transfer promotes cadmium-induced mice nonalcoholic fatty liver disease.

Cadmium (Cd) is an important environmental pollutant. Herein, we discovered a new way of lipid accumulation, where lipid droplets can be transferred across cells. In this study, mice and AML12 cells were used to establish models of Cd poisoning. After Cd treatment, the level of TFAM was reduced, thereby regulating the reconstitution of the cytosolic actin filament network. MYH9 is a myosin involved in cell polarization, migration, and movement of helper organelles. Rab18 is a member of the Rab GTPase family, which localizes to lipid droplets and regulates lipid drop dynamics. In this study, we found that Cd increases the interaction between MYH9 and Rab18. However, TFAM overexpression alleviated the increase in Cd-induced interaction between MYH9 and Rab18, thereby reducing the transfer of intercellular lipid droplets and the accumulation of intracellular lipids. Through a co-culture system, we found that the transferred lipid droplets can act as a signal to form an inflammatory storm-like effect, and ACSL4 can act as an effector to transfer lipid droplets and promote lipid accumulation in surrounding cells. These results suggest that TFAM can be used as a new therapeutic target for Cd-induced lipid accumulation in the liver.

VPS41-mediated incomplete autophagy aggravates cadmium-induced apoptosis in mouse hepatocytes.

Exposure to cadmium (Cd), an environmental heavy metal contaminant, is a serious threat to global health that increases the burden of liver diseases. Autophagy and apoptosis are important in Cd-induced liver injury. However, the regulatory mechanisms involved in the progression of Cd-induced liver damage are poorly understood. Herein, we investigated the role of vacuolar protein sorting 41 (VPS41) in Cd-induced autophagy and apoptosis in hepatocytes. We used targeted VPS41 regulation to elucidate the mechanism of Cd-induced hepatotoxicity. Our data showed that Cd triggered incomplete autophagy by downregulating VPS41, aggravating Cd-induced hepatocyte apoptosis. Mechanistically, Cd-induced VPS41 downregulation interfered with the mTORC1-TFEB/TFE3 axis, leading to an imbalance in autophagy initiation and termination and abnormal activation of autophagy. Moreover, Cd-induced downregulation of VPS41 inhibited autophagosome-lysosome fusion, leading to blocked autophagic flux. This triggers incomplete autophagy, which causes excessive P62 accumulation, accelerating Caspase-9 (CASP9) cleavage. Incomplete autophagy blocks clearance of cleaved CASP9 (CL-CASP9) via the autophagic pathway, promoting apoptosis. Notably, VPS41 overexpression alleviated Cd-induced incomplete autophagy and apoptosis, independent of the homotypic fusion and protein sorting complex. This study provides a new mechanistic understanding of the relationship between autophagy and apoptosis, suggesting that VPS41 is a new therapeutic target for Cd-induced liver damage.

DL-3-N-Butylphthalide Promotes Cartilage Extracellular Matrix Synthesis and Inhibits Osteoarthritis Development by Regulating FoxO3a.

Osteoarthritis (OA) has been reported as a progressive disease in the elderly, primarily characterized by degenerated articular cartilage. There has been no satisfactory drug for the treatment of OA. DL-3-n-butylphthalide (NBP), a small molecule compound extracted from celery seeds, may have antiapoptotic, antioxidant, and anti-inflammatory activities in numerous studies. However, the effects of NBP on OA and its mechanisms have been rarely reported. In this study, the effect of NBP on OA in vitro and in vivo and its possible mechanism were investigated. The results showed that NBP injection into the knee joint inhibited osteoarthritis development in a rat model of osteoarthritis induced by DMM+ACLT. NBP could increase the expressions of extracellular matrix-related components (such as type II collagen, aggrecan, proteoglycan 4, and SRY-box 9) in human osteoarthritic chondrocytes and cartilage explants. Moreover, NBP promoted the expressions of SOD and CAT. NBP upregulated the expression of FoxO3a by inhibiting the PI3K/AKT pathway, which subsequently inhibited the apoptosis of human OA chondrocytes. In conclusion, NBP promotes cartilage extracellular matrix synthesis and inhibits osteoarthritis development and the underlying mechanism related to the activation of FoxO3a.

Gap junction intercellular communication mediates cadmium-induced apoptosis in hepatocytes via the Fas/FasL pathway.

As a common environmental pollutant, cadmium (Cd) causes damage to many organs of the body. Gap junction intercellular communication (GJIC) represents one of the most important routes of rapid signaling between cells. However, the mechanisms underlying GJIC's role in hepatotoxicity induced by Cd remain unknown. We established a Cd poisoning model in vitro by co-culturing Cd-exposed and unexposed hepatocytes and found that 18ß-glycyrrhetinic acid (GA), a GJIC inhibitor, can effectively reduce the apoptosis rate of healthy cells co-cultured with apoptotic cells treated with Cd. We also found that anti-FasL antibody had the same effect. However, in mono-cultured cells, GA treatment in combination with Cd was found to aggravate the damage induced by Cd exposure, increase the level of oxidative stress and protein expression of HO-1, decrease the mitochondrial membrane potential, incur more serious morphological damage to mitochondria than Cd treatment alone. Moreover, compared with Cd-only exposure, GA and Cd co-treatment further increased the expression levels of the apoptosis-related proteins Fas, FasL, FADD and the ratio of Bax/Bcl-2, inhibited the protein expression of ASK1 and Daxx. We also found that the protein expression of Daxx in siFADD + Cd hepatocytes was significantly higher than in Cd-treated cells. Thus, our study suggests that gap junction inhibition may play a dual role in Cd-induced cell damage by inhibiting the transmission of death signals from damaged cells to healthy cells but also aggravating the transmission of death signals between damaged cells, and that the Fas/FasL-mediated death receptor pathway may play an important role in this process.

Case report: A 3-year follow-up study of simultaneous bilateral total hip arthroplasty for Femoral head necrosis in a patient with Kashin-Beck Disease.

Introduction: Kashin-Beck Disease (KBD) is an endemic disease predominantly affecting joint and skeletal muscle, predisposing the articular cartilage to degeneration and necrosis. Currently,staged total hip arthroplasty is a common surgical method for advanced femoral head necrosis from KBD, but there are no reports in the literature on simultaneous bilateral total hip arthroplasty (SB-THA) for patients with KBD. Case presentation: A 42-year-old male from Shaanxi Province, an endemic area, had bilateral hip pain for 4 years, with hips inversion and a crossed gait. After preoperative preparation, a SB-THA was performed by a posterolateral approach. Postoperative medication and functional exercises were administered and the patient was followed up for at least 3 years after discharge. The patient's hip mobility, hip scores and quality of life scores were recorded in detail during the follow-up. Result: The patient stopped antibiotic treatment on the postoperative day-2, and all inflammatory indicators showed normal and started appropriate exercise, and the pain score decreased significantly. On the postoperative day-7, the patient had gradually adapted to various forms of rehabilitation exercises. He was discharged from the hospital on the postoperative day-10 and continued to be followed up. From the preoperative period to the last follow-up, the patient's bilateral hip mobility and functional scores improved significantly, and no adverse events such as hip pain, prosthesis loosening or dislocation were found at the last follow-up. Conclusion: The patient's performance was satisfactory both intraoperatively and in the early postoperative period, but the hip scores and quality of life scores began to plateau or even decline from the third year after surgery to the last follow-up, probably due to the influence of further damage to articular cartilage in other parts of the body.

Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1-PGC-1α pathway activation.

Melatonin is an indoleamine produced in the pineal gland and has many physiological roles. There is increasing evidence that melatonin ameliorates cadmium (Cd)-induced nephrotoxicity. The potential protective impact of melatonin against Cd-induced nephrotoxicity and the mechanisms behind this protection are unknown. The relevance of mitochondrial dynamics in Cd-induced nephrotoxicity and the putative mechanism of melatonin-mediated protection were examined in this study. We show that melatonin prevents Cd-induced nephrotoxicity by inhibiting dynamin-related protein 1 (Drp1)- and mitochondrial fission protein 1 (Fis1)-mediated mitochondrial fission. Melatonin treatment attenuated cytotoxicity, suppressed oxidative stress, restored mitochondrial membrane potential, and increased mitochondrial mass in response to Cd exposure. Consistent with this finding, melatonin treatment increased Cd-inhibited sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) expression and inhibited Drp1- and Fis1-mediated mitochondrial fission. Like melatonin, SIRT1 overexpression via resveratrol attenuated Drp1- and Fis1-mediated mitochondrial fission and other Cd-induced mitochondrial oxidative injuries effectively. Melatonin has significant pharmacological potential for protecting against Cd-induced nephrotoxicity by preventing excessive mitochondrial fission.

Thermosensitive Hydrogel Loaded with Primary Chondrocyte-Derived Exosomes Promotes Cartilage Repair by Regulating Macrophage Polarization in Osteoarthritis.

BACKGROUND: Intra-articular injection is a classic strategy for the treatment of early osteoarthritis (OA). However, the local delivery of traditional therapeutic agents has limited benefits for alleviating OA. Exosomes, an important type of extracellular nanovesicle, show great potential for suppressing cartilage destruction in OA to replace drugs and stem cell-based administration. METHODS: In this study, we developed a thermosensitive, injectable hydrogel by in situ crosslinking of Pluronic F-127 and hyaluronic acid, which can be used as a slow-release carrier to durably retain primary chondrocyte-derived exosomes at damaged cartilage sites to effectively magnify their reparative effect. RESULTS: It was found that the hydrogel can sustainedly release exosomes, positively regulate chondrocytes on the proliferation, migration and differentiation, as well as efficiently induce polarization of M1 to M2 macrophages. Intra-articular injection of this exosomes-incorporated hydrogel significantly prevented cartilage destruction by promoting cartilage matrix formation. This strategy also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+ regenerative M2 macrophages over CD86+ M1 macrophages in synovial and chondral tissue, with a concomitant reduction in pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and increase in anti-inflammatory cytokine (IL-10) in synovial fluid. CONCLUSION: Our results demonstrated that local sustained-release primary chondrocyte-derived exosomes may relieve OA by promoting the phenotypic transformation of macrophages from M1 to M2, which suggesting a great potential for the application in OA.

Biomechanical study of two alternative methods for the treatment of vertical femoral neck fractures - A finite element analysis.

BACKGROUND: No consensus has been reached for the treatment of vertical femoral neck fractures (vFNFs). Recently, two alternative methods were invented to treat vFNFs, one of which is a new plate with a sliding groove, which was designed as a substitution of the medial buttress locking plate to combine with cannulated compression screws (CCS) for reducing the breakage possibility of the proximal locking screw during the bone healing. Another one is the femoral neck system (FNS), which was believed with biomechanical superiority. This study aims to compare the biomechanics of these two new implants with three previous methods via finite element analysis (FEA) to validate whether they are suitable for the treatment of vFNFs. METHODS: Five 70-degree Pauwels type III transcervical FNFs (vFNFs, AO/OTA 31B2.3r) models were built and fixed by CCS augmented with the newly designed sliding groove buttress plate (CCS+BS) and FNS. For comparison, models fixed by three parallel cannulated compression screws (CCS), biplane double-supported screw fixation (BDSF), CCS augmented with a medial buttress locking plate (CCS+BL) were also built. A 2100N load was applied along with the mechanical axis. Parameters of the maximal stress as well as the maximal displacement of the implants and bone, the maximal relative displacement of interfragments, and the stiffness, were analyzed to compare the biomechanical characteristics of the five models. RESULTS: CCS+BS and CCS+BL showed stronger fixation strength with improved stiffness (1012.05N/mm, 1092.04N/mm), reduced maximal displacement of the implants (1.976mm, 1.838mm) and bone (2.075mm, 1.923mm), when compared with CCS (925.11N/mm, 2.158mm and 2.270mm) and BDSF (842.36N/mm, 2.299mm and 2.493mm). While FNS showed the weakest stiffness (593.22N/mm) and largest maximal displacement of the implants (3.234mm) and bone (3.540mm) among the five models. CONCLUSIONS: CCS+BS has a better biomechanical performance than CCS and BDSF, which offers a new choice to deal with vFNFs. The construction stability of FNS is weaker than CCS, BDSF, and CCS+BL, indicating that this method may not as stable as reported in the previous study.

IFN-α-2b Inhibits the Proliferation and Migration of Fibroblasts via the TGFß/Smad Signaling Pathway to Reduce Postoperative Epidural Fibrosis.

Epidural fibrosis after lumbar laminectomy refers to a serious complication, and excessive proliferation of fibroblasts is considered the major factor. Interferon-alpha-2b (IFN-α-2b) can exert antiviral and antiproliferative effects, which has been suggested to effectively prevent several fibrotic diseases. However, the effect of IFN-α-2b on the prevention of epidural fibrosis (EF) and its possible mechanism remain unclear. In this study, in vitro and in vivo experiments were performed to examine the possible mechanism of IFN-α-2b for preventing EF. Cell counting kit-8 (CCK-8), cell cycle test, Edu incorporation, wound healing assay, transwell test, and Western blotting assay were performed to investigate the inhibitory effect of IFN-α-2b on the proliferation and migration of fibroblasts in vitro. As indicated from the results, IFN-α-2b was capable of inhibiting proliferation and migration of fibroblasts and inhibiting the activity of the transforming growth factor ß (TGFß)/Smad signaling pathway. In vivo, the effect of IFN-α-2b on the reduction of EF was determined by performing histological macroscopic evaluation and histological and immunohistochemical staining. As suggested from the results, IFN-α-2b significantly inhibited EF after laminectomy. As revealed from the mentioned results, IFN-α-2b may have a promising application for preventing EF in the future.

Risk factors for femoral neck fracture in elderly population. / è€å¹´è‚¡éª¨é¢ˆéª¨æŠ˜çš„å±é™©å› ç´ .

OBJECTIVES: To explore the risk factors for femoral neck fracture in elderly population. METHODS: A total of 124 elderly patients (≥60 years old) in hospital for trauma were enrolled, including 71 patients (57%) with femoral neck fracture and 53 non-femoral neck fracture patients (43%). All patients' age, gender, body mass index (BMI), bone mineral density (BMD), thigh length and average circumference were collected. Single factor analysis and multivariate logistic regression analysis were performed to explore whether the above factors were risk factors for femoral neck fracture. RESULTS: Single factor analysis showed that the age, gender, BMI, BMD, thigh length, and average thigh circumference between the 2 groups were statistically different (all P<0.05), and multi-factor logistic regression analysis showed that age, gender, BMI, BMD, thigh length, and average thigh circumference were influencing factors for femoral neck fracture in elderly population (all P<0.05). CONCLUSIONS: Older age, female, lower BMI index (low body weight), lower BMD (osteoporosis), longer thigh length, and lower average circumference are risk factors for femoral neck fracture in the elderly population.

Tanshinone IIA regulates fibroblast proliferation and migration and post-surgery arthrofibrosis through the autophagy-mediated PI3K and AMPK-mTOR signaling pathway.

Post-surgery arthrofibrosis is one of the most restrictive factors in the development of intra-articular surgery and has presented tremendous obstacles for most orthopaedic surgeons. Tanshinone IIA (Tan IIA), a key active ingredient of Den-shen, has been used to treat fibrosis-related diseases, such as pulmonary, hepatic and myocardial fibrosis. In the present study, we aimed to investigate the effects of Tan IIA on post-surgery arthrofibrosis in vivo and in vitro. Histological analysis indicated that topical application of Tan IIA (10 mg/mL) could significantly alleviate postsurgery arthrofibrosis in rabbits. Immunohistochemistry results showed that proliferating cell nuclear antigen (PCNA) and tubulin protein expression was inhibited, whereas LC3 was activated in vivo. In vitro, EdU and flow cytometry assays demonstrated that Tan IIA could inhibit fibroblast proliferation by arresting cells in G2 phase. Scratch, Transwell and cytoskeleton protein immunofluorescence assays revealed that fibroblast migration was attenuated. Interestingly, LC3 immunofluorescence staining and transmission electron microscopy indicated that autophagy flux could be induced in fibroblasts by Tan IIA. However, the inhibitory effects of Tan IIA against fibroblast proliferation and migration were partially restored when fibroblast autophagy was suppressed after combined treatment with the autophagy inhibitor 3-methyladenine (3-MA). Finally, the expression of p-mTOR was suppressed in a dose-dependent manner after Tan IIA treatment but partially restored when Tan IIA treatment was combined with 3-MA intervention. The inhibitory effect of Tan IIA against fibroblast proliferation and migration may be related to autophagy induction mediated by the PI3K and AMPK-mTOR signaling pathway.

Treatment of femoral neck fractures: sliding hip screw or cannulated screws? A meta-analysis.

PURPOSE: Femoral neck fractures are still unsolved problems nowadays; sliding hip screw (SHS) and cannulated compression screw (CCS) are the most commonly used devices. We evaluated the clinical outcomes and complications in the treatment of femoral neck fractures between SHS and CCS in this meta-analysis to find which is better. METHODS: We searched PubMed, Embase, Cochrane library up to 24 August 2020 and retrieved any studies comparing sliding hip screw and cannulated compression screw in treatment of femoral neck fractures; the main outcomes and complications were extracted from the studies which were included. RESULTS: Nine studies involving 1662 patients (828 patients in the SHS group and 834 patients in the CCS group) were included in this study. SHS had higher rate of avascular necrosis (RR = 1.30, 95% CI 1.08-1.56, p = 0.005), and CCS had higher rate of implant removal (RR = 0.63, 95% CI 0.43-0.93, p = 0.02). No significant statistical difference in non-union, implant failure, infection, replacement, mortality, orthopedic complications, non-orthopedic complications, and total revision between SHS and CCS group. CONCLUSION: Both devices have their pros and cons; SHS had a higher rate of avascular necrosis, and CCS had a higher rate of implant removal rate. No significant statistical difference in non-union, implant failure, infection, replacement, mortality, orthopedic complications, non-orthopedic complications, and total revision between SHS and CCS group.

Overexpression of laminin α4 facilitates proliferation and migration of fibroblasts in knee arthrofibrosis by targeting canonical Shh/Gli1 signaling.

Aim: Pathologic hyperplasia of fibroblast is responsible for the progression of intraarticular fibrosis. Laminin α4 (LAMA4), a subunit of laminin macromolecule family, was found to be overexpressed in various fibrotic tissues. However, the role of LAMA4 in knee arthrofibrosis remains elusive. Therefore, the aim of this study was to investigate the effect and mechanism of LAMA4 on fibroblast proliferation and migration. Materials and methods: Following knee surgery, LAMA4 expression was detected in intraarticular fibrous tissues in rabbits at week 2 and week 4, respectively. In lentivirus-mediated LAMA4-overexpressed fibroblasts, cellular proliferation was assessed by EdU labeling and cell cycle analysis, cellular migration was evaluated using Transwell assay, and the expressions of key components in Shh/Gli1 signaling were detected by qRT-PCR, western blot and immunofluorescence analysis. Additionally, canonical Shh cascade was further blocked in LAMA4-overexpressed fibroblasts by cyclopamine, and the changes in cellular proliferation and migration were investigated. Results: LAMA4 expression was positively correlated with the severity of knee arthrofibrosis. Functional studies demonstrated that LAMA4 overexpression facilitated proliferation, cell cycle progression and migration in fibroblasts. Mechanically, LAMA4 activated the canonical Shh/Gli1 signaling and promoted the nuclear translocation of Gli1 to upregulate expression of genes associated with cellular proliferation and migration. Intriguingly, blockage of Shh/Gli1 signaling with cyclopamine reversed the promoting effects of LAMA4 on proliferation and migration of fibroblasts. Conclusions: LAMA4 positively regulated cellular proliferation and migration in fibroblasts via activating the Shh/Gli1 signaling. LAMA4/Shh/Gli1 signaling axis might be a potential therapeutic target for the prevention of surgery-induced intraarticular fibrosis.

Unfavorable Contribution of a Tissue-Engineering Cartilage Graft to Osteochondral Defect Repair in Young Rabbits.

A stem cell-based tissue-engineering approach is a promising strategy for treatment of cartilage defects. However, there are conflicting data in the feasibility of using this approach in young recipients. A young rabbit model with an average age of 7.7 months old was used to evaluate the effect of a tissue-engineering approach on the treatment of osteochondral defects. Following in vitro evaluation of proliferation and chondrogenic capacity of infrapatellar fat pad-derived stem cells (IPFSCs) after expansion on either tissue culture plastic (TCP) or decellularized extracellular matrix (dECM), a premature tissue construct engineered from pretreated IPFSCs was used to repair osteochondral defects in young rabbits. We found that dECM expanded IPFSCs exhibited higher proliferation and chondrogenic differentiation compared to TCP expanded cells in both pellet and tissue construct culture systems. Six weeks after creation of bilateral osteochondral defects in the femoral trochlear groove of rabbits, the Empty group (left untreated) had the best cartilage resurfacing with the highest score in Modified O'Driscoll Scale (MODS) than the other groups; however, this score had no significant difference compared to that of 15-week samples, indicating that young rabbits stop growing cartilage once they reach 9 months old. Interestingly, implantation of premature tissue constructs from both dECM and TCP groups exhibited significantly improved cartilage repair at 15 weeks compared to those at six weeks (about 9 months old), indicating that a tissue-engineering approach is able to repair adult cartilage defects. We also found that implanted pre-labeled cells in premature tissue constructs were undetectable in resurfaced cartilage at both time points. This study suggests that young rabbits (less than 9 months old) might respond differently to the classical tissue-engineering approach that is considered as a potential treatment for cartilage defects in adult rabbits.

Everolimus reduces postoperative arthrofibrosis in rabbits by inducing autophagy-mediated fibroblast apoptosis by PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: To investigate the effects of everolimus (EVE) on postoperative fibrosis in the knee joint and the potentially relevant signaling pathways. METHODS: CCK-8 and flow cytometry assays were used to detect the effect of EVE on human fibroblast viability and apoptosis induction. IF and TEM were used to assess fibroblast autophagy. 3-methyladenine (3-MA) was applied to inhibit autophagy to clarify the relationship between autophagy and apoptosis. WB was used to measure the expression of proteins related to apoptosis, autophagy and the mTOR signaling pathway. A rabbit model of knee joint fibrosis was established and topically treated with various concentrations of EVE. IF-P was applied to identify that the main components cells of the fibrotic tissue and histomorphological staining was used to detect the degree of fibrosis and the content of collagen. RESULTS: Histomorphological staining demonstrated that EVE could reduce the degree of postoperative fibrosis and collagen deposition in the knee joint. The results of IF, TEM, flow cytometry assays and WB detection showed that EVE could activate autophagy and induce fibroblasts apoptosis. Meanwhile, the expression levels of p-PI3K, p-Akt, p-mTOR were downregulated with EVE treatment. After the inhibition of autophagy by 3-MA treatment, the increased fibroblasts apoptosis by EVE treatment was partially decreased. CONCLUSION: Everolimus can reduce surgery-induced knee fibrosis by inducing autophagy-mediated fibroblast apoptosis, which may be involved with the regulation of the PI3K/Akt/mTOR signaling pathway.

The efficacy of 3D printing-assisted surgery in treating distal radius fractures: systematic review and meta-analysis.

Aim: To compare the efficacy of 3D printing-assisted surgery with routine surgery in the treatment of distal radius fractures to evaluate whether 3D printing technology has more advantages. Materials & methods: To retrieve all published studies that compared the efficacy of 3D printing-assisted surgery with routine surgery for distal radius fractures. Operation time, frequency of intraoperative fluoroscopy, blood loss and other outcomes were assessed. Results: The results suggested that 3D printing-assisted surgery was better than routine surgery in the fields of operation time, frequency of intraoperative fluoroscopy, and blood loss. Conclusion: In the treatment of distal radius fractures, 3D printing-assisted surgery may be superior to routine surgery.

Intra-articular injection of decellularized extracellular matrices in the treatment of osteoarthritis in rabbits.

BACKGROUND: We investigated the role of decellularized cartilage matrix in osteoarthritis to seek a new treatment for this disease. METHODS: Knee cartilage from rabbits was decellularized and the degree of decellularization was assessed. A grinder was used to turn acellular cartilage into particles, which were then used in a suspension. Thirty New Zealand white rabbits were subjected to an operation on their anterior cruciate ligament for the osteoarthritis model. The success of the animal model of osteoarthritis was evaluated using results from six rabbits. The remaining 24 rabbits were randomly divided into four groups (groups A, B, C, and D). Rabbits in groups A, B, C, and D were injected with 200 µl of normal saline, 200 µl of 10% (w/v) cartilage decellularized suspension, 200 µl of 20% (w/v) cartilage decellularized suspension, and 200 µl of 40% (w/v) cartilage decellularized suspension into the knee joints, respectively. Macroscopic and microscopic assessments were performed three months after surgery to assess the degree of osteoarthritic changes. RESULTS: Histological and biochemical analysis revealed that the cartilage decellularized matrix removed cells after decellularization but retained components of collagen and glycosaminoglycan. Group A exhibited the most significant changes from osteophyte and cartilage erosion, which was macroscopically observable on the surface of the femoral cartilage. HE staining in group A revealed damage to the cartilage surface, disorganized chondrocytes, and spontaneous fibrocartilage formation. Safranin O-fast green staining revealed a cavity formed at the osteochondral junction in group A that did not appear in other groups. CONCLUSION: Our study shows that decellularized cartilage matrix has a certain therapeutic effect on osteoarthritis and provides new insights in the treatment of osteoarthritis.