Mechanisms of vascular invasion after cartilage injury and potential engineering cartilage treatment strategies.

Articular cartilage injury is one of the most common diseases in orthopedic clinics. Following an articular cartilage injury, an inability to resist vascular invasion can result in cartilage calcification by newly formed blood vessels. This process ultimately leads to the loss of joint function, significantly impacting the patient's quality of life. As a result, developing anti-angiogenic methods to repair damaged cartilage has become a popular research topic. Despite this, tissue engineering, as an anti-angiogenic strategy in cartilage injury repair, has not yet been adequately investigated. This exhaustive literature review mainly focused on the process and mechanism of vascular invasion in articular cartilage injury repair and summarized the major regulatory factors and signaling pathways affecting angiogenesis in the process of cartilage injury. We aimed to discuss several potential methods for engineering cartilage repair with anti-angiogenic strategies. Three anti-angiogenic tissue engineering methods were identified, including administering angiogenesis inhibitors, applying scaffolds to manage angiogenesis, and utilizing in vitro bioreactors to enhance the therapeutic properties of cultured chondrocytes. The advantages and disadvantages of each strategy were also analyzed. By exploring these anti-angiogenic tissue engineering methods, we hope to provide guidance for researchers in related fields for future research and development in cartilage repair.

Specific lipid magnetic sphere sorted CD146-positive bone marrow mesenchymal stem cells can better promote articular cartilage damage repair.

BACKGROUND: The characteristics and therapeutic potential of subtypes of bone marrow mesenchymal stem cells (BMSCs) are largely unknown. Also, the application of subpopulations of BMSCs in cartilage regeneration remains poorly characterized. The aim of this study was to explore the regenerative capacity of CD146-positive subpopulations of BMSCs for repairing cartilage defects. METHODS: CD146-positive BMSCs (CD146 + BMSCs) were sorted by self-developed CD146-specific lipid magnetic spheres (CD146-LMS). Cell surface markers, viability, and proliferation were evaluated in vitro. CD146 + BMSCs were subjected to in vitro chondrogenic induction and evaluated for chondrogenic properties by detecting mRNA and protein expression. The role of the CD146 subpopulation of BMSCs in cartilage damage repair was assessed by injecting CD146 + BMSCs complexed with sodium alginate gel in the joints of a mouse cartilage defect model. RESULTS: The prepared CD146-LMS had an average particle size of 193.7 ± 5.24 nm, an average potential of 41.9 ± 6.21 mv, and a saturation magnetization intensity of 27.2 Am2/kg, which showed good stability and low cytotoxicity. The sorted CD146 + BMSCs highly expressed stem cell and pericyte markers with good cellular activity and cellular value-added capacity. Cartilage markers Sox9, Collagen II, and Aggrecan were expressed at both protein and mRNA levels in CD146 + BMSCs cells after chondrogenic induction in vitro. In a mouse cartilage injury model, CD146 + BMSCs showed better function in promoting the repair of articular cartilage injury. CONCLUSION: The prepared CD146-LMS was able to sort out CD146 + BMSCs efficiently, and the sorted subpopulation of CD146 + BMSCs had good chondrogenic differentiation potential, which could efficiently promote the repair of articular cartilage injury, suggesting that the sorted CD146 + BMSCs subpopulation is a promising seed cell for cartilage tissue engineering.

Low-density cultured cartilage cells expanded in platelet lysate present distinct features to develop an innovative clinical treatment for diffuse cartilage lesions.

PURPOSE: Chondrocyte-based cell therapies are effective for the treatment of chondral lesions, but remain poorly indicated for diffuse lesions in the context of early osteoarthritis (OA). The aim of this study was to develop a protocol to obtain chondroprogenitor cells suitable for the treatment of diffuse chondral lesions within early OA. METHODS: Cartilage cells were expanded at low density in human platelet lysate (hPL). A test was performed to exclude senescence. The expression of surface cluster of differentiation 146, cluster of differentiation 166, major histocompatibility complex (MHC)-I and MHC-II and of genes of interest were evaluated, as well as the trophic potential of these cells, by the assessment of lubricin and matrix production. The immunomodulatory potential was assessed through their co-culture with macrophages. RESULTS: Cartilage cells expanded at low density in hPL showed higher proliferation rate than standard-density cells, no replicative senescence, low immunogenicity and expression of lubricin. Moreover, they presented an increased expression of chondrogenic and antihypertrophic markers, as well as a superior matrix deposition if compared to cells cultured at standard density. Cartilage cells induced on macrophages an upregulation of CD206, although a higher increase of CD163 expression was observed in the presence of low-density cells. CONCLUSIONS: These findings lay the grounds to explore the clinical usefulness of low-density cultured cartilage cells to treat diffuse lesions in early OA joints for both autologous and allogenic use. LEVEL OF EVIDENCE: Not applicable.

Influence of cartilage defects and a collagen gel on integrity of corresponding intact cartilage: a biomechanical in-vitro study.

INTRODUCTION: Numerous cartilage repair procedures have been developed for focal lesions to minimize suffering and possibly prevent the development of osteoarthritis with a focus on so-called one-step procedures. The aim of this work was to investigate the effects of both focal cartilage defects and a biomaterial (ChondroFiller) on the corresponding articular cartilage. MATERIALS AND METHODS: On a friction test stand, 18 porcine osteochondral cylinders were tested in six experimental setups under cyclic loading (33 N) against a friction partner in saline solution. The friction partner (cartilage, bone, cartilage defect, cartilage defect with ChondroFiller) and the running times (1 hour and 6 hours) were varied. The damage to the osteochondral cylinders was assessed histologically using a visual damage classification. RESULTS: The cartilage versus bone group showed severe cartilage damage in both the one-hour and six-hour experiments, with an average damage score of 3.5. Damage in the cartilage versus cartilage defect group was moderate, with damage values of 2.5 (1 h) and 2.67 (6 h). The cartilage versus cartilage defect with ChondroFiller group showed a damage value of 2.67 for the one-hour and 2.5 for the six-hour trials. CONCLUSIONS: Even focal grade IV cartilage lesions can lead to significant damage to the corresponding cartilage in vitro. The damage could not be reduced by the use of ChondroFiller, likely because of the initial instability of this biomaterial. Therefore, a biomaterial must be stable in the beginning with regard to full weight-bearing, or joint loading should be delayed until stable filling of the defect is achieved.

Deletion of the chondrocyte glucocorticoid receptor attenuates cartilage degradation through suppression of early synovial activation in murine posttraumatic osteoarthritis.

OBJECTIVE: Disruption of endogenous glucocorticoid signalling in bone cells attenuates osteoarthritis (OA) in aged mice, however, the role of endogenous glucocorticoids in chondrocytes is unknown. Here, we investigated whether deletion of the glucocorticoid receptor, specifically in chondrocytes, also alters OA progression. DESIGN: Knee OA was induced by surgical destabilisation of the medial meniscus (DMM) in male 22-week-old tamoxifen-inducible glucocorticoid receptor knockout (chGRKO) mice and their wild-type (WT) littermates (n = 7-9/group). Mice were harvested 2, 4, 8 and 16 weeks after surgery to examine the spatiotemporal changes in molecular, cellular, and histological characteristics. RESULTS: At all time points following DMM, cartilage damage was significantly attenuated in chGRKO compared to WT mice. Two weeks after DMM, WT mice exhibited increased chondrocyte and synoviocyte hypoxia inducible factor (HIF)-2α expression resulting in extensive synovial activation characterised by synovial thickening and increased interleukin-1 beta expression. At 2 and 4 weeks after DMM, WT mice displayed pronounced chondrocyte senescence and elevated catabolic signalling (reduced Yes-associated protein 1 (YAP1) and increased matrix metalloprotease [MMP]-13 expression). Contrastingly, at 2 weeks after DMM, HIF-2α expression and synovial activation were much less pronounced in chGRKO than in WT mice. Furthermore, chondrocyte YAP1 and MMP-13 expression, as well as chondrocyte senescence were similar in chGRKO-DMM mice and sham-operated controls. CONCLUSION: Endogenous glucocorticoid signalling in chondrocytes promotes synovial activation, chondrocyte senescence and cartilage degradation by upregulation of catabolic signalling through HIF-2α in murine posttraumatic OA. These findings indicate that inhibition of glucocorticoid signalling early after injury may present a promising way to slow osteoarthritic cartilage degeneration.

Meniscal allograft transplantation improves patient-reported outcomes in both minimal and moderate knee osteoarthritis at 1 and 2 years postoperatively.

PURPOSE: Severe cartilage damage and advanced knee osteoarthritis (OA) might be associated with poor outcomes of meniscal allograft transplantation (MAT). The purpose of this prospective follow-up study was to explore MAT survivorship and patient satisfaction among young patients with symptomatic meniscal deficiency and radiological OA of different Kellgren-Lawrence (K-L) grades. METHODS: Thirty-five consecutive MAT patients were prospectively followed up for 2 years. The lateral meniscus was replaced in 29 patients and the medial meniscus in 6 patients. Outcomes were assessed using the KOOS4 composite score, KOOS subscales, Lysholm knee score, and OA K-L grade progression from weight-bearing knee radiographs. For the outcome analysis, patients were categorized into two groups: 19 in Group A (K-L classification 0-1) and 16 in Group B (K-L classification 2). RESULTS: In terms of KOOS4 and Lysholm scores, the patients showed a clinically significant improvement from baseline to the 1-year follow-up (22.2 points, 95% CI 16.6-27.8 for KOOS4 and 16.8 points, 95% CI 8.9-24.6 for Lysholm), and the improvement remained at 2 years (20.6 points, 95% CI 13.2-28.1 for KOOS4 and 21.5, 95% CI 12.5-30.7 for Lysholm). At the 6-month follow-up, this improvement was not yet observed. Minor between-group differences were observed in the KOOS4 and Lysholm scores for the K-L 0-1 and K-L 2 OA groups, but the estimates were imprecise with wide confidence intervals. A clinically relevant difference between these two study groups could not be found at any timepoint. The reoperation rate was higher in the K-L 2 group than in the K-L 0-1 group (31% vs. 11%). CONCLUSIONS: MAT yielded improved patient-reported outcomes and subjective satisfaction at 1 and 2 years postoperatively. The differences from baseline exceeded the minimal clinically important difference (MCID) at all timepoints. The severity of cartilage damage and knee OA in terms of the K-L grade at the time of surgery did not affect the KOOS and Lysholm scores after the MAT procedure. Knee OA progression in terms of K-L grade worsening was not observed in any patients. LEVEL OF EVIDENCE: III.

Patellofemoral articular cartilage damage is associated with poorer patient-reported outcomes following isolated medial patellofemoral ligament reconstruction.

PURPOSE: The purpose of this study was to investigate the impact of articular cartilage damage on outcomes following medial patellofemoral ligament (MPFL) reconstruction. METHODS: Record review identified 160 patients who underwent isolated MPFL reconstruction at a single institution between 2008 and 2016. Patient demographics, patellofemoral articular cartilage status at surgery, and patient anatomical measures from imaging were obtained via chart review. Patients were contacted and outcomes assessed through collection of Norwich Patellar Instability (NPI) score, Knee injury and Osteoarthritis Outcome Score (KOOS), and Marx activity score as well as an assessment for recurrent patellar dislocation. Outcomes of patients with grade 0-II patellofemoral cartilage damage were compared to those of patients with grade III-IV cartilage damage. RESULTS: One hundred twenty-two patients (76%) with a minimum of one year follow-up were contacted at a mean of 4.8 years post-operatively. A total of 63 patients (52%) had grade III or IV patellofemoral chondral damage at the time of surgery. The majority of the defects was on the medial patella (46 patients-72%) and the mean patellar defect size was 2.8 cm2. Among 93 patients who completed patient-reported outcome scores, the 52 with grade III or IV chondral damage reported a significantly poorer KOOS Quality of Life than the 44 patients with grade 0 to II chondral damage (p = 0.041), controlling for patient age, sex, BMI, and anatomical factors. CONCLUSION: Patients with grade III or IV articular cartilage damage of the patellofemoral joint at the time of MPFL reconstruction demonstrated poorer KOOS knee-related quality of life than patients without grade III or IV articular cartilage damage at a mean of 4.8 years following isolated MPFL reconstruction. LEVEL OF EVIDENCE: Level II.

Synovial mesenchymal stem cell-derived exosomal microRNA-320c facilitates cartilage damage repair by targeting ADAM19-dependent Wnt signalling in osteoarthritis rats.

OBJECTIVE: Our previous study revealed that synovial mesenchymal stem cell (SMSC)-derived exosomal microRNA-302c enhanced chondrogenesis by targeting a disintegrin and metalloproteinase 19 (ADAM19) in vitro. This study aimed to validate the potential of SMSC-derived exosomal microRNA-302c for the treatment of osteoarthritis in vivo. METHODS: After 4 weeks of destabilization of the medial meniscus surgery (DMM) to establish an osteoarthritis model, the rats received weekly articular cavity injection of SMSCs with or without GW4869 treatment (exosome inhibitor) or exosomes from SMSCs with or without microRNA-320c overexpression for another 4 weeks. RESULTS: SMSCs and SMSC-derived exosomes reduced the Osteoarthritis Research Society International (OARSI) score, improved cartilage damage repair, suppressed cartilage inflammation, suppressed extracellular matrix (ECM) degradation, and inhibited chondrocyte apoptosis in DMM rats. However, these effects were largely hampered in rats that were injected with GW4869-treated SMSCs. Moreover, exosomes from microRNA-320c-overexpressing SMSCs exerted a better effect than exosomes from negative control SMSCs on decreasing the OARSI score, enhancing cartilage damage repair, suppressing cartilage inflammation, and inhibiting ECM degradation and chondrocyte apoptosis. Mechanistically, exosomes from microRNA-320c-overexpressing SMSCs reduced the levels of ADAM19, as well as ß-catenin and MYC, which are two critical proteins in Wnt signalling. CONCLUSION: SMSC-derived exosomal microRNA-320c suppresses ECM degradation and chondrocyte apoptosis to facilitate cartilage damage repair in osteoarthritis rats by targeting ADAM19-dependent Wnt signalling.

Mitochondrial quality control in cartilage damage and osteoarthritis: new insights and potential therapeutic targets.

Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality of life in the elderly population. Although the prevalence of OA increases with age, its specific mechanisms have not been elucidated and effective therapeutic disease-modifying drugs have not been developed. As essential organelles in chondrocytes, mitochondria supply energy and play vital roles in cellular metabolism, proliferation and apoptosis. Mitochondrial quality control (MQC) is the key mechanism to coordinate various mitochondrial biofunctions, primarily through mitochondrial biogenesis, dynamics, autophagy and the newly discovered mitocytosis. An increasing number of studies have revealed that a loss of MQC homeostasis contributes to the cartilage damage during the occurrence and development of OA. Several master MQC-associated signaling pathways and regulators exert chondroprotective roles in OA, while cartilage damage-related molecular mechanisms have been partially identified. In this review, we summarized known mechanisms mediated by dysregulated MQC in the pathogenesis of OA and latent bioactive ingredients and drugs for the prevention and treatment of OA through the maintenance of MQC.

From Cells to Organs: The Present and Future of Regenerative Medicine.

Regenerative medicine promises a bright future where damaged body parts can be restored, rejuvenated, and replaced. The application of regenerative medicine is interdisciplinary and covers nearly all fields of medical sciences and molecular engineering. This review provides a road map on how regenerative medicine is applied on the levels of cell, tissue, and organ and summarizes the advantages and limitation of human pluripotent stem cells in disease modeling and regenerative application.

Quadriceps strength is negatively associated with knee joint structural abnormalities-data from osteoarthritis initiative.

OBJECTIVE: The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA). METHODS: This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45-79. Quadriceps strength was measured by isometric knee extension testing at baseline. Knee joint structural abnormalities, including cartilage damage, bone marrow lesions (BMLs), effusion-synovitis and Hoffa-synovitis, were evaluated by Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) at baseline and 1-year follow-up. Generalized estimating equations were employed to examine the associations between quadriceps strength and knee structural abnormalities. All analyses were stratified by sex. RESULTS: One thousand three hundred thirty-eight participants (523 men and 815 women) with a mean age of 61.8 years and a mean BMI of 29.4 kg/m2 were included in this study. For men, no significantly longitudinal association of quadriceps strength with structural abnormalities was detected. In contrast, quadriceps strength was significantly and negatively associated with changes in cartilage damage and BMLs in lateral patellofemoral joint (PFJ) (cartilage damage: OR: 0.91, 95% CI 0.84 to 0.99, P = 0.023; BMLs: OR: 0.85, 95% CI 0.74 to 0.96, P = 0.011) and effusion-synovitis (OR = 0.88, 95% CI 0.78 to 0.99, P = 0.045) among females longitudinally. Higher quadriceps strength was significantly associated with less progression of lateral PFJ cartilage damage, BMLs and effusion-synovitis in females. CONCLUSIONS: Higher quadriceps strength was associated with changes in cartilage damage and BMLs within the lateral PFJ and effusion-synovitis among females, suggesting the potential protective role of quadriceps strength on joint structures in women.

Animal models of Kashin-Beck disease exposed to environmental risk factors: Methods and comparisons.

The main etiological mechanism for Kashin-Beck disease (KBD) is deep chondrocyte necrosis induced by environmental risk factors (ERFs). The scholars have conducted several epidemiological, cellular, and animal model studies on ERFs. Gradually, four etiological hypotheses have been formed, including water of organic poisoning hypothesis represented by fulvic acid (FA), biogeochemical hypothesis represented by selenium (Se) deficiency, food mycotoxin poisoning hypothesis represented by T-2 toxin poisoning and compound etiology theory hypothesis. The animal models of KBD have been replicated based on the previous etiological hypotheses. The different species of animals (monkey, rat, dog, pig, chicken, and rabbit) were treated with different ERFs interventions, and the clinical manifestations and pathological changes of articular cartilages were observed. The animals in the experimental group were fed with endemic water, endemic grain, low nutrition, thallium sulfate, FA, Se, T-2 toxin, and iodine. The dose of thallium sulfate was 1154 µg/d; the doses range of FA were 5, 50, 150, 200, and 211 mg/kg; the doses range of Se were 0.00035, 0.00175, 0.005, 0.02, 0.031, 0.1, 0.15, 0.314, 0.5, and 10 mg/kg; the doses range of T-2 toxin were 40, 100, 200, 600, 1000, 1500, 3000, 6000, and 9000 ng/g; and the doses range of iodine were 0.04, 0.18, and 0.4-0.5 µg/g. The sample size ranged from 9 to 230 depending on the interventions and grouping; the follow-up duration ranged from 1 week to 18 months. Moreover, the methods and comparisons of different animal models of KBD had been summarized to provide a useful basis for studying the pathogenesis of KBD. In conclusion, the rhesus monkeys administrated endemic water and grain were susceptible animals to replicate KBD. The rats treated with T-2 toxin combined with Se/nutrition deficiency could be a suitable and widely used animal model.

Slight cartilage damage in weight-bearing area of lateral femoral condyle do not compromise short-term outcomes of medial unicompartmental knee arthroplasty.

INTRODUCTION: Medial unicompartmental knee arthroplasty (mUKA) requires full-thickness cartilage in the lateral compartment, but slight damage of the cartilage surface can be ignored. However, as this statement lacks literature support, we investigated whether slight cartilage damages in the weight-bearing area of the lateral femoral condyle would affect the outcome of mUKAs. MATERIALS AND METHODS: Outerbridge grading was performed on the cartilage in the weight-bearing area of the lateral femoral condyle intraoperatively. The patients, grouped as normal or as having lateral condyle cartilage of Outerbridge grade 1-2 (slight cartilage damage), underwent mUKA. Full-length lower extremity radiographs were taken and hip-knee-ankle angles (HKAAs) were measured both preoperatively and postoperatively. Using magnetic resonance imaging, the lateral meniscal extrusion distance was also measured. In addition, the Oxford Knee Score (OKS) was assessed preoperatively and at the last follow-up, in addition to the patient satisfaction assessment. RESULTS: We enrolled 152 knees of 142 patients proposed for mUKAs. The mean age of participants was 69.5 years (51-89 years) and they were followed up for a mean of 25.4 months (15-44 months). There was no significant difference in preoperative (p = 0.746) and postoperative (p = 0.202) mean OKS between the normal, Outerbridge grade 1 and Outerbridge grade 2 groups. While the normal group had a higher change in OKS than the group with cartilage damage, this difference was not significant (p = 0.910). The UKA corrected the patients' mean HKAA from 171.1° (preoperatively) to 176.1° (postoperatively). From all patients, only four had slight lateral meniscus extrusion with MEDs of ≤ 0.25 mm. With the exception of one patient with a poor outcome in normal group, the rest were satisfied with the outcome of mUKA. No patients had prosthesis-related complications or revision surgery. CONCLUSIONS: Cartilage damage of Outerbridge grade 1 and grade 2 in the weight-bearing area of the lateral femoral condyle will not compromise the short-term outcome of medial mobile-bearing UKA.

PLCγ1 inhibition-driven autophagy of IL-1ß-treated chondrocyte confers cartilage protection against osteoarthritis, involving AMPK, Erk and Akt.

Previous studies identified the involvement of phosphoinositide-specific phospholipase C (PLC) γ1 in some events of chondrocytes. This study aims to investigate whether and how PLCγ1 modulates autophagy to execute its role in osteoarthritis (OA) progression. Rat normal or human OA chondrocytes were pretreated with IL-1ß for mimicking or sustaining OA pathological condition. Using Western blotting, immunoprecipitation, qPCR, immunofluorescence and Dimethylmethylene blue assays, and ELISA and transmission electron microscope techniques, we found that PLCγ1 inhibitor U73122 enhanced Collagen II, Aggrecan and GAG levels, accompanied with increased LC3B-II/I ratio and decreased P62 expression level, whereas autophagy inhibitor Chloroquine partially diminished its effect. Meanwhile, U73122 dissociated Beclin1 from Beclin1-IP3R-Bcl-2 complex and blocked mTOR/ULK1 axis, in which the crosstalk between PLCγ1, AMPK, Erk and Akt were involved. Additionally, by haematoxylin and eosin, Safranin O/Fast green, and immunohistochemistry staining, we observed that intra-articular injection of Ad-shPLCγ1-1/2 significantly enhanced Collagen and Aggrecan levels, accompanied with increased LC3B and decreased P62 levels in a rat OA model induced by anterior cruciate ligament transection and medial meniscus resection. Consequently, PLCγ1 inhibition-driven autophagy conferred cartilage protection against OA through promoting ECM synthesis in OA chondrocytes in vivo and in vitro, involving the crosstalk between PLCγ1, AMPK, Erk and Akt.

Synovial mesenchymal stem cell-derived extracellular vesicles containing microRN555A-26a-5p ameliorate cartilage damage of osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease characterized by cartilage damage. We aimed to improve the understanding of the protective mechanism of synovial mesenchymal stem cell (SMSC)-derived extracellular vesicles (EVs) in cartilage damage of OA. METHODS: SMSCs and SMSC-EVs were isolated from synovial biopsies of patients without OA and then identified. The pathological microenvironment of chondrocytes in OA was simulated by inducing SW1353 cells with interleukin (IL)-1ß, followed by SMSC-EV treatment to assess SW1353 cell proliferation, apoptosis and inflammation. Endocytosis of Dil-labeled EVs by SW1353 cells was observed. microRNA (miR)-26a-5p expression in EVs and EV-treated SW1353 cells was assessed. The effect of miR-26a-5p was evaluated after it was down-regulated in SMSCs, followed by extraction of EVs, which acted on SW1353 cells. The target relationship of miR-26a-5p and phosphatase and tensin homologue (PTEN) was predicted and confirmed. The role of PTEN in OA was evaluated after it was overexpressed. Functional assays were implemented in vivo to certify the role of SMSC-EVs in OA. RESULTS: SMSC-EVs enhanced IL-1ß-induced SW1353 cell proliferation, whereas they inhibited apoptosis and inflammation. EVs were endocytosed by SW1353 cells and delivered miR-26a-5p into SW1353 cells to overexpress miR-26a-5p. Down-regulation of miR-26a-5p in EVs attenuated the protection of EVs against IL-1ß-induced cell damage. miR-26a-5p targeted PTEN, for which overexpression spoiled the protection of EVs against IL-1ß-induced cell damage. SMSC-EVs carrying miR-26a-5p repaired cartilage damage of OA. CONCLUSIONS: SMSC-EVs carried miR-26a-5p into chondrocytes to up-regulate miR-26a-5p and inhibit PTEN, thereby inhibiting apoptosis and inflammation and ameliorating cartilage damage of OA.

Alteration of the gut microbiota in rhesus monkey with spontaneous osteoarthritis.

BACKGROUND: The spontaneous osteoarthritis (OA) in rhesus macaque is similar to OA in human, which maintains an upright body posture and shows very similar biomechanical properties of bones to humans. At present, there is no good treatment for OA. This study aims to explore relationship between OA and intestinal microbiota, and provide a reference for the treatment of clinical OA. RESULTS: We collected colonic contents of the 20 rhesus macaque (6-15 years old, female) for intestinal microbiota analysis by metagenomics sequencing, of which 10 were spontaneous OA monkeys and 10 were normal monkeys. Our results showed the diversity of gut microbiota in monkeys with OA was decreased compared to the normal monkeys (p = 0.16). Mollicutes, Tenericutes, Coprobacillus and Faecalitalea may be biomarkers for the monkeys of OA. Lactobacillus found significantly increased in OA monkeys. Prevotella and Ruminococcus were higher in the normal group than OA group. Zinc/manganese transport system permease protein (p = 0.0011) and Cyclopropane-fatty-acyl-phospholipid synthase (p = 0.0012) are a microbiota metabolic pathway related to cartilage production. CONCLUSIONS: Our results indicate that the diversity and composition of intestinal microbiota in monkeys with OA are different compared to the normal monkeys. we have found microbes that may be a biomarker for the diagnosis of osteoarthritis. Functional analysis of the microbiota also predicts cartilage damage in the monkeys with osteoarthritis. Non-human primates are closely related to humans, so this study can provide a reference for the development of drugs for the treatment of OA.

Spectroscopic photoacoustic imaging of cartilage damage.

OBJECTIVE: Osteoarthritis (OA) is a chronic joint disease characterized by progressive degradation of cartilage. It affects more than 10% of the people aged over 60 years-old worldwide with a rising prevalence due to the increasingly aging population. OA is a major source of pain, disability, and socioeconomic cost. Currently, the lack of effective diagnosis and affordable imaging options for early detection and monitoring of OA presents the clinic with many challenges. Spectroscopic Photoacoustic (sPA) imaging has the potential to reveal changes in cartilage composition with different degrees of damage, based on optical absorption contrast. DESIGN: In this study, the capabilities of sPA imaging and its potential to characterize cartilage damage were explored. To this end, 15 pieces of cartilage samples from patients undergoing a total joint replacement were collected and were imaged ex vivo with sPA imaging at a wide optical spectral range (between 500 nm and 1,300 nm) to investigate the photoacoustic properties of cartilage tissue. All the PA spectra of the cartilage samples were analyzed and compared to the corresponding histological results. RESULTS: The collagen related PA spectral changes were clearly visible in our imaging data and were related to different degrees of cartilage damage. The results are in good agreement with histology and the current gold standard, i.e., the Mankin score. CONCLUSIONS: This study demonstrates the potential and possible clinical application of sPA imaging in OA.

An acquired plica-induced notch in the medial femoral condyle in a patient with medial patellar plica syndrome: a case report.

BACKGROUND: An inflamed and thickened medial patellar plica (MPP) caused by repeated mechanical irritation from trauma or overuse leads to impingement between the anterior medial femoral condyle and the medial articular facet of the patella and produces pain or clicking, which is known as MPP syndrome. In patients with MPP syndrome, cartilage damage may occur depending on the shape of the MPP and the duration of the impingement. CASE PRESENTATION: Preoperative magnetic resonance imaging in a 17-year-old male patient with MPP syndrome showed a hypertrophic MPP along with an abnormal notch in the articular surface of the medial femoral condyle. We considered that the impinged hypertrophic plica between the anterior medial femoral condyle and the medial articular facet of the patella resulted in cartilage damage on the articular surface of the medial femoral condyle. However, during arthroscopic surgery, we found that the cartilage of the notch, which was located beneath the MPP, was completely intact. We concluded that this abnormal notch had developed gradually in the MPP without cartilage damage. CONCLUSIONS: Surgeons should be mindful that acquired plica-induced notches in the articular surface of the medial femoral condyle can present in patients with MPP syndrome.

Matrix-induced chondrogenesis is a valid and safe cartilage repair option for small- to medium-sized cartilage defects of the knee: a systematic review.

PURPOSE: The purpose of this study was to perform a systematic review of randomized controlled trials comparing the results of matrix-induced chondrogenesis with other therapies for local chondral lesions of the knee. METHODS: A systematic search for randomized controlled trials (RCT) about matrix-induced chondrogenesis for focal chondral lesions in the knee was performed according to the PRISMA guidelines. Data source was PubMed central, EMBASE and Google scholar. RESULTS: Five articles could be included, whereas two originated from the same study group. Three studies compared matrix-induced chondrogenesis to microfracture (MFx) only. One trial compared AMIC® to collagen-covered autologous chondrocyte implantation (ACI-C). One study assessed the improvements given by the combination of AMIC® with bone marrow aspirate concentrate (BMAC). In three studies, clinical improvements compared to baseline were seen at 2-year postoperation, irrespective of the technique used. After 5 years, one trial showed better results for the AMIC® group compared to MFx, including MRI defect filling. One study showed also good results after AMIC® with faster recovery for patients with AMIC® + BMAC 12 months postoperatively. CONCLUSION: Results of RCTs comparing matrix-induced chondrogenesis with other treatment options showed that matrix-induced chondrogenesis is a valid and safe cartilage repair option for small- to medium-sized cartilage defects of the knee. This one-stage surgical technique presents a good alternative for patients. LEVEL OF EVIDENCE: I.

Arrabidaea chica Verlot fractions reduce MIA-induced osteoarthritis progression in rat knees.

This study aims to investigate the activity of n-hexane, ethyl acetate and butanol fractions obtained from Arrabidaea chica Verlot against MIA-induced osteoarthritis (OA). The antinociceptive potentials of each fraction were evaluated through a cyclooxygenase (COX) 1 and 2 inhibition test and an in vivo OA-model. In addition, toxicity assessments in the liver, spleen and kidney, as well as radiographic and histopathological knee analyses, were performed. The chemical composition of the n-hexane fraction was elucidated, and a molecular docking protocol was carried out to identify which compounds are associated with the detected bioactivity. The n-hexane A. chica fraction preferentially inhibits COX-2, with 90% inhibition observed at 10 µg/mL. The fractions also produced significant improvements in OA incapacity, motor activity and hyperalgesia parameters and in radiological knee conditions. However, concerning the histopathological evaluations, these improvements were only significant in the hexane and ethyl acetate fraction treatments, which resulted in better average scores, suggesting that these fractions slow OA-promoted joint injury progression. Histopathological organ analyses indicate that the fractions are not toxic to animals. Twenty compounds were identified in the n-hexane fraction, comprising fatty acids, terpenes and phytosterols. In silico analyses indicate the presence of favourable interactions between some of the identified compounds and the COX-2 enzyme, mainly concerning alpha-tocopherol (Vitamin E), squalene and beta-sitosterol. The findings indicate that A. chica fractions display analgesic, anti-inflammatory properties, are non-toxic and are able to slow OA progression, and may, therefore, be prioritized as natural products in OA human clinical trials.