miR-182 promotes cervical cancer progression via activating the Wnt/ß-catenin axis.

Cervical cancer (CC) is among the leading causes of cancer-associated mortality in women worldwide; yet the molecular regulators involved in its progression are unclear. This study found that miR-182 was overexpressed in CC tissues when compared with adjacent normal tissues. Moreover, it found that miR-182 expression was significantly positively correlated with distant metastasis in patients with CC. Interestingly, in vitro experiments showed that overexpression and inhibition of miR-182 promoted and suppressed the growth of CC cells, respectively. The tumor-promoting effects of miR-182 on CC progression were achieved via the Wnt/ß-catenin axis and its downstream genes. Thus, this study revealed the potential of miR-182/ß-catenin as an effective new target for CC treatment.

[Retracted] MicroRNA­124 acts as a tumor­suppressive miRNA by inhibiting the expression of Snail2 in osteosarcoma.

[This retracts the article DOI: 10.3892/ol.2018.7994.].

Cryo-EM structure of human heptameric pannexin 2 channel.

Pannexin 2 (Panx2) is a large-pore ATP-permeable channel with critical roles in various physiological processes, such as the inflammatory response, energy production and apoptosis. Its dysfunction is related to numerous pathological conditions including ischemic brain injury, glioma and glioblastoma multiforme. However, the working mechanism of Panx2 remains unclear. Here, we present the cryo-electron microscopy structure of human Panx2 at a resolution of 3.4 Å. Panx2 structure assembles as a heptamer, forming an exceptionally wide channel pore across the transmembrane and intracellular domains, which is compatible with ATP permeation. Comparing Panx2 with Panx1 structures in different states reveals that the Panx2 structure corresponds to an open channel state. A ring of seven arginine residues located at the extracellular entrance forms the narrowest site of the channel, which serves as the critical molecular filter controlling the permeation of substrate molecules. This is further verified by molecular dynamics simulations and ATP release assays. Our studies reveal the architecture of the Panx2 channel and provide insights into the molecular mechanism of its channel gating.

The Risk Factors for New-Onset Calf Muscle Venous Thrombosis after Hip Fracture Surgery.

BACKGROUND: Calf muscle venous thrombosis (CMVT) is among the most important medical complications after hip surgery. CMVT has been known for many years, but many opinions about the incidence and risk factors of CMVT are still controversial. The objective of this retrospective study was to investigate the incidence and associated risk factors of postoperative CMVT in patients with hip fractures. METHODS: Patients with hip fractures from January 2020 to April 2022 (n = 320) at Shenzhen Second People's Hospital were recruited in this study. The personal characteristics and clinical data of CMVT and no-CMVT patients were compared and analyzed. Binary logistic regression analyses were performed to identify potential risk factors of CMVT in patients with hip fractures. Finally we performed a receiver operating characteristic (ROC) curve analysis to compare the diagnostic values of different variables. RESULTS: The overall incidence of new-onset CMVT in patients with hip fractures was 18.75% (60 of 320). Among the 60 CMVT patients, 70% (42 of 60) were diagnosed with femoral neck fractures, 28.3% (17 of 60) with intertrochanteric fractures, and 1.7% (1 of 60) with subtrochanteric fractures. No pulmonary embolism (PE) occurred. High preoperative D-dimer (OR = 1.002, 95%CI 0.97-1.03), sex (OR = 1.22, 95%CI 0.51-2.96), the caprini score (OR = 2.32, 95%CI 1.05-5.16) and the waterlow score (OR = 1.077, 95%CI 0.35-3.36) significantly increased the risk of developing postoperative new-onset CMVT. CONCLUSIONS: CMVT has become a common clinical disease, and its harm should not be underestimated. Our study found that D-dimer, sex, the caprini score and the waterlow score were independent risk factors for postoperative CMVT. According to our clinical work, we should pay attention to identifying the risk factors of CMVT formation and targeted intervention measures to prevent new-onset CMVT.

Large-scale Preparation of Synovial Fluid Mesenchymal Stem Cell-Derived Exosomes by 3D Bioreactor Culture.

Exosomes secreted by mesenchymal stem cells (MSCs) have been suggested as promising candidates for cartilage injuries and osteoarthritis treatment. Exosomes for clinical application require large-scale production. To this aim, human synovial fluid MSCs (hSF-MSCs) were grown on microcarrier beads, and then cultured in a dynamic three-dimension (3D) culture system. Through utilizing 3D dynamic culture, this protocol successfully obtained large-scale exosomes from SF-MSC culture supernatants. Exosomes were harvested by ultracentrifugation and verified by a transmission electron microscope, nanoparticle transmission assay, and western blotting. Also, the microbiological safety of exosomes was detected. Results of exosome detection suggest that this approach can produce a large number of good manufacturing practices (GMP)-grade exosomes. These exosomes could be utilized in exosome biology research and clinical osteoarthritis treatment.

ANLN and UBE2T are prognostic biomarkers associated with immune regulation in breast cancer: a bioinformatics analysis.

OBJECTIVES: To screen and verify differential genes affecting the prognosis of breast cancer. METHODS: Breast cancer gene expression datasets were downloaded from the GEO database, and original data were analyzed in R. The TIMER database was used to analyze the relationship between ANLN and UBE2T and immune cell infiltration. RESULTS: Ten hub-key genes were identified, and survival analysis showed that UBE2T and ANLN were upregulated in breast cancer and their upregulation was associated with a poor prognosis. ANLN and UBE2T upregulation was associated with the prevalence of Th1 and Th2 cells, shifting the Th1/Th2 balance to Th2 in Basal and Luminal-B breast cancers, which indicates a poor prognosis (P < 0.05). CONCLUSION: ANLN and UBE2T are potential biomarkers for predicting the prognosis of breast cancer.

Insights into the implementation of Fibronectin 1 in the cartilage tissue engineering.

Recently, cartilage tissue engineering has become a cornerstone to treat cartilage degeneration and osteoarthritis (OA). Fibronectin1 (FN1) is described as multiple functional glycoproteins that play an essential role in chondrogenic and osteogenic differentiation. Few studies reported the potential of FN1 to enhance tissue engineering and reduce the death of chondrocytes in OA. Further, FN1 possesses multiple binding domains including collagen, integrin, and heparin that can interact with heparan sulfate proteoglycans at the surface of chondrocyte leading to promote cell signaling and differentiation. Recent studies suggested that FN1 can promote chondrocyte differentiation by upregulating TGF-ß/PI3K/Akt pathways. Further, FN1 can inhibit the apoptosis of chondrocytes by preventing the release of metalloproteinases through lowering the expression of p-PI3K/PI3K and p-AKT/AKT pathways. However, the use of FN1 in cartilage repair studies using animal models or clinical trials was rarely reported. Therefore, this article provides new insights into the importance of FN1 in cartilage tissue engineering to encourage more studies concerning FN1 in cartilage repair studies. Further, we provided new suggestions for advanced applications of FN1 to treat OA and cartilage degeneration.

Indoleamine 2, 3 Dioxygenase 1 Impairs Chondrogenic Differentiation of Mesenchymal Stem Cells in the Joint of Osteoarthritis Mice Model.

Osteoarthritis (OA) is a serious joint inflammation that leads to cartilage degeneration and joint dysfunction. Mesenchymal stem cells (MSCs) are used as a cell-based therapy that showed promising results in promoting cartilage repair. However, recent studies and clinical trials explored unsatisfied outcomes because of slow chondrogenic differentiation and increased calcification without clear reasons. Here, we report that the overexpression of indoleamine 2,3 dioxygenase 1 (IDO1) in the synovial fluid of OA patients impairs chondrogenic differentiation of MSCs in the joint of the OA mice model. The effect of MSCs mixed with IDO1 inhibitor on the cartilage regeneration was tested compared to MSCs mixed with IDO1 in the OA animal model. Further, the mechanism exploring the effect of IDO1 on chondrogenic differentiation was investigated. Subsequently, miRNA transcriptome sequencing was performed for MSCs cocultured with IDO1, and then TargetScan was used to verify the target of miR-122-5p in the SF-MSCs. Interestingly, we found that MSCs mixed with IDO1 inhibitor showed a significant performance to promote cartilage regeneration in the OA animal model, while MSCs mixed with IDO1 failed to stimulate cartilage regeneration. Importantly, the overexpression of IDO1 showed significant inhibition to Sox9 and Collagen type II (COL2A1) through activating the expression of ß-catenin, since inhibiting of IDO1 significantly promoted chondrogenic signaling of MSCs (Sox9, COL2A1, Aggrecan). Further, miRNA transcriptome sequencing of SF-MSCs that treated with IDO1 showed significant downregulation of miR-122-5p which perfectly targets Wnt1. The expression of Wnt1 was noticed high when IDO1 was overexpressed. In summary, our results suggest that IDO1 overexpression in the synovial fluid of OA patients impairs chondrogenic differentiation of MSCs and cartilage regeneration through downregulation of miR-122-5p that activates the Wnt1/ß-catenin pathway.

Arthroscopic acetabular labrum reconstruction with capsular autograft: clinical outcome and preliminary results.

To introduce a novel technique to reconstruct the acetabular labrum using capsular autograft, and to evaluate the preliminary clinical outcome, a retrospective review of a prospectively collected registry was undertaken that identified 21 patients (21 hips) who underwent arthroscopic reconstruction of the labrum by capsular autograft from January 2016 to January 2018. Modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), and Hip Outcome Score-Activities of Daily Living (HOS-ADL) were recorded preoperatively and postoperatively. Clinical outcome was analyzed to evaluate the effectiveness of this technique. Twenty-one patients, with an average follow-up time of 25.4 ± 1.6 months, were included in this study: 7 patients were diagnosed with hypoplastic labrum (width <5 mm), 9 patients with complex tear of labrum, and 5 patients with degenerative labrum. The mHHS (61.3 ± 5.5 vs. 87.5 ± 4.2, P<0.001), HOS (52.5 ± 5.1 vs. 87.3 ± 3.8, P<0.001) and HOS-ADL (48.5 ± 5.8% vs. 75.2 ± 3.5%, P<0.001) between preoperative and the 6-month follow-up were significantly different. Gender exerts no influence on the outcome of mHHS, HOS and HOS-ADL. Therefore, local capsular autograft is readily available during arthroscopy with no donor-site morbidity. The reconstruction of the hip labrum may be valuable for patients with hypoplastic or dysplastic labrum, complex tear of labrum and severe degeneration. With appropriate patient selection, this technique is promising in preliminary clinical outcome.

Crosstalk between immune cells and bone cells or chondrocytes.

The term "osteoimmunology" was coined to denote the bridge between the immune system and the skeletal system. Osteoimmunology is interdisciplinary, and a full understanding and development of this "bridge" will provide an in-depth understanding of the switch between body health and disease development. B lymphocytes can promote the maturation and differentiation of osteoclasts, and osteoclasts have a negative feedback effect on B lymphocytes. Different subtypes of T lymphocytes regulate osteoclasts in different directions. T lymphocytes have a two-way regulatory effect on osteoblasts, while B lymphocytes have minimal regulatory effects on osteoblasts. In contrast, osteoblasts can promote the differentiation and maturation of T lymphocytes and B lymphocytes. Different immune cells have different effects on chondrocytes; some cooperate with each other, while some antagonize each other. In a healthy adult body, bone resorption and bone formation are in a dynamic balance under the action of multiple mechanisms. In this review, we summarize the interactions and key signaling molecular mechanisms between each type of cell in the immune system and the skeletal system.

Light-induced osteogenic differentiation of BMSCs with graphene/TiO2 composite coating on Ti implant.

Light-induced surface potential have been demonstrated as an effective bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation regulator. However, traditional bone repair implants almost were weak or no light-responsive. Fortunately, surface modification was a feasible strategy to realize its light functionalization for bone implants. Herein, a graphene oxide (GO)/titanium dioxide (TiO2) nanodots composite coating on the surface of titanium (Ti) implant was constructed, and GO was reduced to reduced graphene oxide (rGO) with the method of UV-assisted photocatalytic reduction. After rGO deposited on the surface of TiO2, a heterojunction formed at the interface of rGO and TiO2. With visible light illumination, positive charges accumulated on the surface of rGO/TiO2 film, and performed as a positive surface potential change. The light-induced surface potential which was generated under proper light intensity is harmless to the cell adhesion and proliferation behavior, but presented a good BMSCs osteogenic differentiation promoting effect, and the activation of the voltage-gated calcium channels through surface potential and the promotion of the adsorption of osteogenic growth factors could be the reason. This work given a new insight of the modification for Ti implant with a light-induced surface potential, and shows potential application for bone regeneration on the clinical practice through light stimulation.

3D printed gelatin/hydroxyapatite scaffolds for stem cell chondrogenic differentiation and articular cartilage repair.

Acute injury of the articular cartilage can lead to chronic disabling conditions because of the limited self-repair capability of the cartilage. Implantation of stem cells at the injury site is a viable treatment, but requires a scaffold with a precisely controlled geometry and porosity in the 3D space, high biocompatibility, and the capability of promoting chondrogenic differentiation of the implanted stem cells. Here we report the development of gelatin/hydroxyapatite (HAP) hybrid materials by microextrusion 3D bioprinting and enzymatic cross-linking as the scaffold for human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). The scaffold supports the adhesion, growth, and proliferation of hUCB-MSCs and induces their chondrogenic differentiation in vitro. Doping HAP in the gelatin scaffold increases the fluidity of the hydrogel, improves the gelation kinetics and the rheological properties, and allows better control over 3D printing. Implanting the hUCB-MSC-laden scaffold at the injury site of the articular cartilage effectively repairs the cartilage defects in a pig model. Altogether, this work demonstrates the 3D printing of gelatin-based scaffold materials for hUCB-MSCs to repair cartilage defects as a potential treatment of articular cartilage injury.

High expression of MAPK-14 promoting the death of chondrocytes is an important signal of osteoarthritis process.

BACKGROUND: Osteoarthritis (OA) is one of the most common degenerative diseases worldwide. Many researchers are studying the pathogenesis of OA, however, it is still unclear. METHODS: Screening and validation of OA relevant hub genes are an important part of exploring their potential molecular mechanism. Therefore, this study aims to explore and verify the mechanisms of hub genes in the OA by bioinformatics, qPCR, fluorescence and propidium iodide staining. RESULTS: Microarray datasets GSE43923, GSE55457 and GSE12021 were collected in the Gene Expression Omnibus (GEO), including 45 samples, which divided into 23 osteoarthritis knee joint samples and 22 samples of normal knee joint. Thereafter, 265 differentiallyexpressedgenes (DEGs) were identified in all, which divided into 199 upregulated genes and 66 downregulated genes. The hub genes MAPK-14, PTPRC, PTPN12 were upregulated, while B9D1 was downregulated. In order to further confirm the expression of screening differential genes in human chondrocytes, the human chondrocytes were extracted from a joint replacement surgery and stained with toluidine blue for identification. Compared with normal chondrocytes, OA chondrocytes had high expression of COL I protein and low expression of COL II protein. The expression levels of MAPK-14, PTPRC and PTPN12 in OA chondrocytes were significantly higher than the expression levels of B9D1 in normal chondrocytes. Moreover, the inflammatory necrosis of OA chondrocytes was increased compared with the normal chondrocytes by propidium iodide staining. CONCLUSIONS: The high expression of MAPK-14 works as a promoter of chondrocytes death and an important signal of the osteoarthritis process.

Forecasting sensitive targets of the kynurenine pathway in pancreatic adenocarcinoma using mathematical modeling.

In this study, a new mathematical model was established and validated to forecast and define sensitive targets in the kynurenine pathway (Kynp) in pancreatic adenocarcinoma (PDAC). Using the Panc-1 cell line, genetic profiles of Kynp molecules were tested. qPCR data were implemented in the algorithm programming (fmincon and lsqnonlin function) to estimate 35 parameters of Kynp variables by Matlab 2017b. All tested parameters were defined as non-negative and bounded. Then, based on experimental data, the function of the fmincon equation was employed to estimate the approximate range of each parameter. These calculations were confirmed by qPCR and Western blot. The correlation coefficient (R) between model simulation and experimental data (72 hours, in intervals of 6 hours) of every variable was >0.988. The analysis of reliability and predictive accuracy depending on qPCR and Western blot data showed high predictive accuracy of the model; R was >0.988. Using the model calculations, kynurenine (x3, a6), GPR35 (x4, a8), NF-kßp105 (x7, a16), and NF-kßp65 (x8, a18) were recognized as sensitive targets in the Kynp. These predicted targets were confirmed by testing gene and protein expression responses. Therefore, this study provides new interdisciplinary evidence for Kynp-sensitive targets in the treatment of PDAC.

Arthroscopic repair of the medium-size rotator cuff tear with the novel technique of the point union bridge: a minimum 2-year follow-up cohort study.

BACKGROUND: Achieving secure fixation and preventing retear have been recognized as fundamental in arthroscopic repair of rotator cuff tears. Moreover, reducing internal implantation can lower medical expenses and minimize the operation time, which is essential for the surgical safety and postoperative rehabilitation of the patients. We have recently proposed the point union bridge (PUB) suture configuration as a novel method for not only providing equivalent fixation but also decreasing the operation time and medical expenses. However, no comparative clinical studies have been performed. METHODS: From March 2014 to September 2016, a total of 88 patients with diagnoses of medium-size rotator cuff tears underwent arthroscopic repair with a randomly assigned technique-either the PUB technique (n = 42) or the double-row suture bridge (DRSB) technique (n = 46). All patients underwent a minimal 2-year follow-up. We used the Constant-Murley score (CMS), American Shoulder and Elbow Surgeons (ASES) score, active and passive range of motion, and visual pain-simulation score (visual analog scale [VAS] score) to assess the functional outcomes. In addition, we recorded the arthroscopic operation time, medical costs, and postoperative complications. All patients received magnetic resonance imaging at the 6-month and 2-year postoperative evaluations to assess structural integrity and tendon healing. RESULTS: At the 2-year follow-up, all scoring parameters evaluated (CMS, ASES score, and VAS score), as well as active and passive range of motion, improved significantly in both groups as compared with preoperative assessments. The PUB technique significantly decreased the operation time (55.9 ± 14.1 minutes vs. 72.2 ± 14.2 minutes for PUB vs. DRSB, P < .001) and medical expenses ($2608.0 ± $391.1 vs. $4056.9 ± $350.9 for PUB vs. DRSB, P < .001). However, no significant differences between the 2 techniques were found in any functional assessments of the shoulder (CMS, ASES score, and VAS score), repair integrity, or the retear rate at the 2-year follow-up. CONCLUSION: Arthroscopic repair of the medium-size rotator cuff tear with either the PUB or DRSB technique could yield both satisfactory improvements in the shoulder function of patients and equivalent tendon integrity. With less consumption of internal implants, the PUB technique significantly reduced the operation time and decreased medical expenses.

Expression of LRRC8A is elevated in the cytoplasm of osteosarcoma tissues: An immunohistochemical study with tissue microarrays.

The purpose of the present study was to investigate the expression profile of leucine-rich repeat-containing protein 8A (LRRC8A) in osteosarcoma and normal cortical bone, as well as its association with sex, age and tumor malignancy. Immunohistochemical staining of osteosarcoma tissue microarrays (TMAs) was performed to determine the protein expression of LRRC8A and compare them among different subgroups. The expression of LRRC8A in the nuclei and cytoplasm of U2OS tumor cells and MC3T3-E1 osteoblast-like cells was determined using reverse transcription-quantitative PCR. Of all samples of the TMA for patients with osteosarcoma that were tested, 94% featured high cytoplasmic expression of LRRC8A, while in all normal bone tissue control groups, the gene was mainly expressed in the nucleus. In MC3T3-E1 osteoblasts, the expression of LRRC8A at the RNA level was mainly in the cytoplasm. The difference in expression of LRRC8A between microarrays and osteoblasts was statistically significant. In U2OS osteosarcoma cells, LRRC8A mRNA was concentrated in the nuclei and cytoplasm. In osteosarcoma, the expression level of LRRC8A was not significantly associated with sex or age. In conclusion, LRRC8A was highly expressed in the cytoplasm of osteosarcoma cells and the degree of expression may be associated with the degree of tumor malignancy.

Pathological changes of frozen shoulder in rat model and the therapeutic effect of PPAR-γ agonist.

Frozen shoulder is a common shoulder disorder characterized by a gradual increase of pain and a limited range of motion. However, its pathophysiologic mechanisms remain unclear and there is no consensus as to the most effective treatment. The purpose of the study was to investigate the effect of transforming growth factor-ß (TGF-ß) on fibrosis and inflammatory response of the shoulder joint of rat models and to explore the therapeutic effect of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist. In the study, the effect of PPAR-γ agonist CDDO-IM treatment on cell proliferation, migration, and extracellular matrix proteins synthesis (vimentin, α-smooth muscle actin, collagen I, and collagen III) were tested by cell proliferation test, scratches test, real-time quantitative polymerase chain reaction, and Western blot analysis. The frozen shoulder was also established on the rat model by injecting adenovirus-TGF-ß1 into rats' shoulder capsule. Pathological changes of the frozen shoulder tissue of the experimental group and PPAR-γ agonist treatment group were evaluated. The stiffness of joints of the three groups was tested. Inflammatory mediators' expression including cyclooxygenase-1, interleukin-1ß, and tumor necrosis factor-α of the shoulder was tested by enzyme-linked immunosorbent assay, and the expression of extracellular matrix proteins was evaluated by hematoxylin and eosin staining and immunohistochemistry. The results showed that pathological changes of the frozen shoulder in the rat model include an abnormal proliferation of fibroblasts, infiltration of inflammatory cells, and disorder of fibrous structure, while rosiglitazone reduced the severity of the frozen shoulder in the treatment group. Clinically, PPAR-γ agonists may be a promising target for the treatment of the frozen shoulder.

Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration.

Transplantation of synovial fluid-derived mesenchymal stem cells (SF-MSCs) is a viable therapy for cartilage degeneration of osteoarthritis (OA). But controlling chondrogenic differentiation of the transplanted SF-MSCs in the joints remains a challenge. Kartogenin (KGN) is a small molecule that has been discovered to induce differentiation of SF-MSCs to chondrocytes both in vitro and in vivo. The clinical application of KGN however is limited by its low water solubility. KGN forms precipitates in the cell, resulting in low effective concentration and thus limiting its chondrogesis-promoting activity. Here we report that targeted delivery of KGN to SF-MSCs by engineered exosomes leads to even dispersion of KGN in the cytosol, increases its effective concentration in the cell, and strongly promotes the chondrogenesis of SF-MSCs in vitro and in vivo. Fusing an MSC-binding peptide E7 with the exosomal membrane protein Lamp 2b yields exosomes with E7 peptide displayed on the surface (E7-Exo) that has SF-MSC targeting capability. KGN delivered by E7-Exo efficiently enters SF-MSCs and induces higher degree of cartilage differentiation than KGN alone or KGN delivered by exosomes without E7. Co-administration of SF-MSCs with E7-Exo/KGN in the knee joints via intra-articular injection also shows more pronounced therapeutic effects in a rat OA model than KGN alone or KGN delivered by exosomes without E7. Altogether, transplantation of SF-MSCs with in situ chondrogenesis enabled by E7-Exo delivered KGN holds promise towards as an advanced stem cell therapy for OA.

Effects of ATP9A on Extracellular Vesicle Release and Exosomal Lipid Composition.

Numerous biological processes are regulated by the intercellular communications arising from extracellular vesicles (EVs) released from cells. However, the mechanisms that regulate the quantity of EV discharged have yet to be understood. While it is known that ATP9A, a P4-ATPase, is involved in endosomal recycling, it is not clear whether it also contributes to the release of EVs and the makeup of exosomal lipids. This study is aimed at exploring the role of human ATP9A in the process of EV release and, further, to analyze the profiles of EV lipids regulated by ATP9A. Our results demonstrate that ATP9A is located in both the intracellular compartments and the plasma membrane. The percentage of ceramides and sphingosine was found to be significantly greater in the control cells than in the ATP9A overexpression and ATP9A knockout groups. However, EV release was greater in ATP9A knockout cells, indicating that ATP9A inhibits the release of EVs. This study revealed the effects of ATP9A on the release of EVs and the lipid composition of exosomes.

Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy.

Targeted delivery to the diseased cell or tissue is the key to the successful clinical use of nucleic acid drugs. In particular, delivery of microRNA-140 (miRNA-140, miR-140) into chondrocytes across the dense, nonvascular extracellular matrix of cartilage remains a major challenge. Here, we report the chondrocyte-targeting exosomes as vehicles for the delivery of miR-140 into chondrocytes as a new treatment for osteoarthritis (OA). By fusing a chondrocyte-affinity peptide (CAP) with the lysosome-associated membrane glycoprotein 2b protein on the surface of exosomes, we acquire CAP-exosomes that can efficiently encapsulate miR-140, specifically enter, and deliver the cargo into chondrocytes in vitro. CAP-exosomes, in contrast to nontagged exosome vesicles, are retained in the joints after intra-articular injection with minimal diffusion in vivo. CAP-exosomes also deliver miR-140 to deep cartilage regions through the dense mesochondrium, inhibit cartilage-degrading proteases, and alleviate OA progression in a rat model, pointing toward a potential organelle-based, cell-free therapy of OA.