Knee Articular Cartilage Research Articles

Association of Postoperative Lateral Meniscal Extrusion With Cartilage Degeneration on Magnetic Resonance Imaging After Discoid Lateral Meniscus Reshaping Surgery.

Background:Although arthroscopic reshaping surgery for a discoid lateral meniscus (DLM) has good clinical results, it cannot completely prevent degeneration. The degree of DLM extrusion associated with degenerative changes is unclear.Purpose/Hypothesis:To measure meniscal extrusion preoperatively and postoperatively in patients who underwent DLM-reshaping surgery and examine factors associated with knee articular cartilage degeneration. It was hypothesized that meniscal extrusion existed preoperatively, progressed postoperatively, and was related to knee joint degeneration.Study Design:Case-control study; Level of evidence, 3.Methods:We retrospectively reviewed the medical records of patients who underwent DLM-reshaping surgery and attended ≥2 years of follow-up. Magnetic resonance imaging (MRI) was performed preoperatively and at 24 months postoperatively, and residual midbody meniscal extrusion was measured. Cartilage degeneration was detected when the Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the lateral compartment was grade ≥3 at 2 years postoperatively. Factors associated with MRI cartilage degeneration were evaluated.Results:Included in this study were 48 knees in 39 patients; the mean patient age at the time of surgery was 12.0 years. The mean midbody meniscal extrusion significantly increased from 0.8 mm preoperatively to 1.6 mm at 24 months postoperatively (P < .001). According to the WORMS cartilage score, 16 patients were categorized as having MRI cartilage degeneration. Multivariate logistic analysis showed that an inferior preoperative Lysholm score (odds ratio, 0.89; P = .024) and postoperative extrusion (odds ratio, 6.18; P = .010) significantly increased the risk of cartilage degeneration. The receiver operating characteristic curve showed that a residual meniscal extrusion of 2.0 mm was the cutoff value indicating cartilage degeneration (sensitivity, 87.5%; specificity, 78.1%).Conclusion:DLM extrusion significantly increased from 0.8 mm preoperatively to 1.6 mm at 2 years postoperatively. Postoperative extrusion and a lower preoperative Lysholm score were factors related to MRI cartilage degeneration postoperatively. A postoperative extrusion of 2.0 mm was the cutoff value for MRI cartilage degeneration.

WITHDRAWN: Brucine restores sodium nitroprusside-induced chondrocyte dysfunction by suppressing the GSK-3β/β-catenin pathway

The dysfunction of chondrocytes is thought to play a role in the initiation and progression of osteoarthritis (OA). Brucine possesses wide pharmacological activities. But the protective mechanism of the brucine on chondrocytes remains unclear. This study is aimed to determine the therapeutic effects of brucine on the mouse chondrocyte OA model by sodium nitroprusside (SNP). The primary chondrocytes were obtained from the knee articular cartilage of a healthy suckling mouse donor. The cultured chondrocytes were divided into the control group, SNP group, brucine group, brucine-SNP group, brucine-SNP-GSK-3β antagonist group (brucine-SNP- group), and brucine-SNP-GSK-3β agonist group (brucine-SNP-GSK-3β+ group). After 24 h, the chondrocytes from different treated groups were collected to detect chondrocyte proliferation and ultrastructure, regulation factors, apoptosis, oxidative stress, and GSK-3β/β-catenin pathway. Compared to the SNP group, chondrocyte proliferation, and regulation factors were promoted, and chondrocyte apoptosis, oxidative stress, and the GSK-3β/β-catenin pathway were inhibited by brucine. It indicates that the adverse effect of SNP is reversed by the brucine on the chondrocyte. Compared to the brucine-SNP group, the effect of brucine on the chondrocyte proliferation, regulation factothe apoptosis, and oxidative stress were promoted by the GSK-3β antagonist. It indicates that the chondrocyte is protected agairucine through buying the GSK-3β/β-catenin pathway.

Platelet-Rich Plasma and Adipose-Derived Mesenchymal Stem Cells in Association with Arthroscopic Microfracture of Knee Articular Cartilage Defects: A Pilot Randomized Controlled Trial.

Background This study aims to compare the effects of platelet-rich plasma (PRP) alone or in combination with adipose-derived mesenchymal stem cells (AD-MSCs) in patients affected by cartilage defects, undergoing knee arthroscopic microfracture. Methods Thirty-eight patients diagnosed with a knee monocompartmental cartilage defect (Outerbridge grade IV) on the MRI, underwent an arthroscopic procedure. After the confirmation of the lesion, they all received the same bone marrow stimulation technique (microfracture) and were randomized into two groups: the first one had additional PRP injection (group A), while the second received PRP and AD-MSC injection (group B). Knee assessment and pain score were documented with Knee Injury Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, Short-Form (SF) 12, and Visual Analogue Scale (VAS) before the treatment and at 1, 3, 6, and 12 months of follow-up postoperatively. An additional arthroscopic procedure, performed in four patients for a subsequent meniscal lesion, let us evaluate cartilage evolution by performing a macro/microscopical assessment on cartilage biopsy specimens. Results At the 12-month follow-up, both groups showed a comparable functional improvement. The scores on the IKDC form, KOOS, pain VAS, and SF-12 significantly improved from baseline (p < 0.05) to 12 months postoperatively in both treatment groups. The four second-look arthroscopies showed a complete repair of the articular defects by smooth solid cartilage layer, with a good chondrocytic population, in both groups. A thick smooth hyaline-like cartilage with a predominantly viable cell population and normal mineralization (a form closely resembling native tissue) was observed in group B. Conclusions Modern regenerative medicine techniques, such as PRP and AD-MSC, associated with traditional arthroscopic bone marrow stimulating techniques, seem to enhance cartilage restoration ability. The preliminary results of this pilot study encourage the synergic use of these regenerative modulating systems to improve the quality of the regenerated cartilage.

Matrix-assisted autologous chondrocyte transplantation for treatment of focal chondral lesions in the knee: the Hospital Israelita Albert Einstein experience.

ABSTRACTObjective Phase 1 clinical trial to determine feasibility, safety, and efficacy of a new advanced cell therapy product for treatment of knee articular cartilage injuries.Methods Three participants with knee focal chondral lesions were included, with no signs of osteoarthritis. Chondrocytes were obtained through knee arthroscopy, cultured in collagen membrane for 3 weeks at the laboratory, subjected to tests to release the cell therapy product, and implanted. All patients underwent a specific 3-month rehabilitation protocol, followed by assessments using functional and imaging scales. The main outcome was the incidence of severe adverse events.Results Three participants were included and completed the 2-year follow-up. There was one severe adverse event, venous thrombosis of distal leg veins, which was no associated with therapy, was treated and left no sequelae. The clinical and radiological scales showed improvement in the three cases.Conclusion The preliminary results, obtained with the described methodology, allow concluding that this product of advanced cell therapy is safe and feasible. ReBEC platform registration number: RBR-6fgy76

Seahorse Protein Hydrolysate Ameliorates Proinflammatory Mediators and Cartilage Degradation on Posttraumatic Osteoarthritis with an Obesity Rat Model.

Osteoarthritis (OA) is one of the age-related diseases and is highly present on the knees. Obesity and mechanical injuries as a risk factor of OA are attributed to cartilage disintegration, joint loading, and inflammation. This study is aimed at investigating the effects of seahorse protein hydrolysate (SH) on posttraumatic osteoarthritis in an obesity rat. The OA model was developed by anterior cruciate ligament transection with medial meniscectomy in a high-fat diet- (HFD-) induced obesity rat model. The male Sprague-Dawley rats were fed a HFD for 6 weeks before OA surgery. The OA rats were treated with oral gavage by 4, 8, or 20 mg/kg of body weight of SH for 6 weeks of treatment. The expressions of plasma proinflammatory factors, C-telopeptide of type II collagen, and matrix metalloproteinase- (MMP-) 3 and MMP-13 were reduced by SH treatment. Plasma superoxide dismutase and glutathione peroxidase activities were enhanced by SH. SH also relieved the pain of the knee joint and swelling as well as decreased proteoglycan loss in the knee articular cartilage caused by osteoarthritis. Based on these results, SH suppressed proinflammatory factors and attenuated cartilage degradation and pain in the OA model. Therefore, seahorse protein hydrolysate might be a potential opportunity for improving the development of osteoarthritis.

Evaluation of articular cartilage in knee osteoarthritis using hybrid multidimensional MRI

To evaluate a two-compartment model with a normal and an abnormal compartment using hybrid multidimensional (HM) magnetic resonance imaging (MRI) for detection of early stage degeneration in knee articular cartilage. Forty mild osteoarthritis (OA; Kellgren-Lawrence grades [KLGs] 1 and 2), 27 moderate OA (KLG 3), and 23 healthy controls were included in the study. HM imaging using a two-compartment model was used to measure a normal and an abnormal cartilage compartment. The relationship between Vnormal and the degree of cartilage degeneration was examined using whole-organ MRI scores (WORMS). Receiver operating characteristic analysis was used to detect the ability of Vnormal, apparent diffusion coefficient (ADC), and T2 relaxation time to discriminate healthy controls from early OA. The intra- and interobserver reproducibility for calculated mean Vnormal values and WORMS indicated substantial agreement (intraclass correlation coefficient and weighted kappa >0.8). Overall, Vnormal in all compartments significantly differed among the healthy controls (50±5.5%) and mild (41.1±5.3%) and moderate OA (36.4±8.1%). Mean Vnormal correlated negatively with the degree of OA progression (ρ=-0.778, p<0.001). Mean Vnormal was characterised by a higher sensitivity (82.5%, 95% confidence interval [CI=67.2-92.7) and specificity (87%, 95% CI=66.4-97.2), with a cut-off value of 44.4%, compared to ADC and T2 values or a combination of ADC and T2 to differentiate early OA from healthy controls. HM-MRI coupled with values of ADC and T2 may provide value for detecting cartilage degeneration at an early stage of OA.

Global Variation in Studies of Articular Cartilage Procedures of the Knee: A Systematic Review.

ObjectiveThe objective of this study was to determine whether there are significant differences in terms of indications, techniques, patient variables, and objective and subjective outcome scores as a function of the geographic locale of published studies of knee articular cartilage surgery.MethodsAn electronic database search was performed of clinical studies evaluating knee articular cartilage procedures from 2000 to 2021. Studies were separated into global regions (Europe, Asia, North America, and South America) based on the study country. All cartilage-based treatments in each region were recorded. Patient age and sex, mechanism of injury, cartilage lesion size and location, follow-up time, failure rate, and knee outcome scores utilized were summarized and compared by region.ResultsA total of 2,923 studies were analyzed. Eighty level 1 and 2 studies met the inclusion criteria. The majority were from Europe (n = 60), followed by Asia (n = 11), North America (n = 7), and South America (n = 2). The majority of procedures in European and North American studies were cell-based and marrow-stimulation procedures. In Asian studies, the most common procedures were marrow-stimulation, experimental, and biologic procedures as defined by the authors. Asian countries had a higher proportion of females (P < 0.001) and an overall older patient population (P < 0.001). Regional variation was also seen in terms of lesion location, mechanism of injury, and failure rate.ConclusionMost high-level evidence for articular cartilage-based procedures of the knee comes from European countries. These studies vary by patient age and sex, anatomic location, and mechanism of injury. Global variation should be taken into consideration when interpreting and applying studies of knee articular cartilage surgery.

Lateral collagen meniscus implant (CMI): techniques and outcomes-a narrative review.

The menisci increase the stability of the tibio-femoral joint, distribute axial load, absorb shock, and provide nutrition and lubrification to the knee articular cartilage. Therefore, is it clear the importance of the meniscus on the overall knee function and the need to preserve it during arthroscopic surgery. However, according to many registry databases, meniscectomy is still the most performed meniscus surgery. In a percentage of patients, knee pain and swelling, as well as bone edema on the tibial plateau, could follow meniscus resection; this constellation of symptoms is known as "post-meniscectomy syndrome". If this syndrome is not promptly managed, a rapid worsening of the symptoms and develop of knee osteoarthritis could be expected. While dealing with such condition, the clinician must perform first an accurate clinical examination and a full radiological evaluation. If the patient is candidate for surgery, the replacement of the resected tissue should be performed: a meniscus allograft should be implanted in case of previous total meniscectomy or a meniscus scaffold if the patients has an history of a previous partial resection. The present article represents a comprehensive review of the literature and aims to discuss basic science, preoperative planning and evaluation, indication, surgical technique, and outcomes of the lateral collagen meniscus implant (CMI), a biologic scaffold aimed at replacing partial meniscal defects.

Stem Cells Promote the Regeneration of Knee Joint Degenerative Bone and Articular Cartilage.

Cartilage damage has a certain ability to spontaneously repair, but the repaired tissue often shows the phenomenon of cartilage terminal differentiation, which causes irreversible damage to its structure and function and seriously affects the quality of life and work of patients. It is of great significance to study the problems encountered in the process of cartilage damage repair. This article mainly studied stem cells to promote the regeneration of knee joint degenerative bone articular cartilage. First, the animal articular cartilage defect is modeled, 10 ml of animal venous blood is drawn, 0.5 ml of PRP is collected by centrifugation, mixed with cartilage fragments, and transplanted into the defect area into a gel. In the BMSCs group, 1 ml of BMSCs with a cell concentration of 107 cells/ml was injected intra-articularly. The histological chromosomes were observed after 6 weeks and 12 weeks, and the effect of cartilage tissue repair was analyzed and evaluated, and the related data were statistically analyzed. We evaluated the spontaneous repair ability of partial cartilage damage, full-thickness cartilage damage, and osteochondral damage. Furthermore, for partial cartilage damage repair, by using the cartilage damage in vitro model and biomaterials to simulate the in vivo microenvironment, the adhesion and cell morphology on the surface of partial- and full-thickness cartilage damage were evaluated, and the experiments were further used to evaluate the exogenous and internal induced migration effect of source on cultured cells in vitro. In the cell concentration study, the cartilage repair effect increased with the increase in concentration within a certain range, and the tissue repair ability remained stable when the concentration exceeded 107 cells/ml. Using ECM-oriented scaffolds to compound autologous BMSCs, tissue-engineered cartilage was successfully constructed, which had the histological and biochemical characteristics of normal cartilage tissue, and better repaired the damaged articular cartilage of large animals.

Saikosaponin D Inhibited IL-1β Induced ATDC 5 Chondrocytes Apoptosis In Vitro and Delayed Articular Cartilage Degeneration in OA Model Mice In Vivo.

Osteoarthritis (OA) is the most common joint disease in the elderly, characterized by cartilage degradation and proliferation of subchondral bone. The pathogenesis of OA involves a variety of inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. From the molecular mechanism, the nuclear factor-erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway and the expression of ROS regulated the production of the above inflammatory mediators. Saikosaponin D (SSD), which is an active ingredient isolated from Bupleurum, has various biological functions. In this study, IL-1β was used as a pro-inflammatory factor to create an in vitro OA model. According to the results of high-density culture, qPCR, ROS measurement, Western blot, and immunofluorescence, SSD activated the Nrf2/HO-1/ROS axis, inhibited the production of inflammatory mediators, and protected against ECM destruction. The DMM mouse model was used as a model of OA in mice. From the results of safranin O/fast green staining, hematoxylin–eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and OARSI scores, SSD protected against the mice knee articular cartilage degeneration and reduced the number of osteoclasts in the subchondral bone. Experimental results found that SSD suppressed IL-1β–induced differentiated ATDC 5 chondrocytes apoptosis via the Nrf2/HO-1/ROS axis in vitro. SSD delayed the progression of OA in DMMs model mice in vivo. Therefore, SSD has the potential to become a drug for clinical treatment of OA.

Effect of silk fibroin microcarrier loaded with clematis total saponins and chondrocytes on promoting rabbit knee articular cartilage defects repair

To prepare the silk fibroin microcarrier loaded with clematis total saponins (CTS) (CTS-silk fibroin microcarrier), and to investigate the effect of microcarrier combined with chondrocytes on promoting rabbit knee articular cartilage defects repair. CTS-silk fibroin microcarrier was prepared by high voltage electrostatic combined with freeze drying method using the mixture of 5% silk fibroin solution, 10 mg/mL CTS solution, and glycerin. The samples were characterized by scanning electron microscope and the cumulative release amount of CTS was detected. Meanwhile, unloaded silk fibroin microcarrier was also prepared. Chondrocytes were isolated from knee cartilage of 4-week-old New Zealand rabbits and cultured. The 3rd generation of chondrocytes were co-cultured with the two microcarriers respectively for 7 days in microgravity environment. During this period, the adhesion of chondrocytes to microcarriers was observed by inverted phase contrast microscope and scanning electron microscope, and the proliferation activity of cells was detected by cell counting kit 8 (CCK-8), and compared with normal cells. Thirty 3-month-old New Zealand rabbits were selected to make bilateral knee cartilage defects models and randomly divided into 3 groups ( n=20). Knee cartilage defects in group A were not treated, and in groups B and C were filled with the unloaded silk fibroin microcarrier-chondrocyte complexes and CTS-silk fibroin microcarrier-chondrocyte complexes, respectively. At 12 weeks after operation, the levels of matrix metalloproteinase 9 (MMP-9), MMP-13, and tissue inhibitor of MMP 1 (TIMP-1) in articular fluid were detected by ELISA. The cartilage defects were collected for gross observation and histological observation (HE staining and toluidine blue staining). Western blot was used to detect the expressions of collagen type Ⅱ and proteoglycan. The inflammatory of joint synovium was observed by histological staining and inducible nitric oxide synthase (iNOS) immunohistochemical staining. The CTS-silk fibroin microcarrier was spherical, with a diameter between 300 and 500 μm, a porous surface, and a porosity of 35.63%±3.51%. CTS could be released slowly in microcarrier for a long time. Under microgravity, the chondrocytes attached to the surface of the two microcarriers increased gradually with the extension of culture time, and the proliferation activity of chondrocytes at 24 hours after co-culture was significantly higher than that of normal chondrocytes ( P<0.05). There was no significant difference in proliferation activity of chondrocytes between the two microcarriers ( P>0.05). In vivo experiment in animals showed that the levels of MMP-9 and MMP-13 in group C were significantly lower than those in groups A and B ( P<0.05), and the level of TIMP-1 in group C was significantly higher ( P<0.05). Compared with group A, the cartilage defects in groups B and C were filled with repaired tissue, and the repaired surface of group C was more complete and better combined with the surrounding cartilage. Histological observation and Western blot analysis showed that the International Cartilage Repair Scoring (ICRS) and the relative expression levels of collagen type Ⅱ and proteoglycan in groups B and C were significantly better than those in group A, and group C was significantly better than group B ( P<0.05). The histological observation showed that the infiltration of synovial inflammatory cells and hyperplasia of small vessels significantly reduced in group C compared with groups A and B. iNOS immunohistochemical staining showed that the expression of iNOS in group C was significantly lower than that in groups A and B ( P<0.05). CTS-silk fibroin microcarrier has good CTS sustained release effect and biocompatibility, and can promote the repair of rabbit cartilage defect by carrying chondrocyte proliferation in microgravity environment.

High resolution T2∗ mapping in assessment of knee articular cartilage on 3T MRI

ObjectiveTo evaluate the spectrum of T2∗ values in healthy cartilage of young asymptomatic adults on high resolution 3T MRI. MethodsA total of 50 asymptomatic adult volunteers with age ranging from 18 to 35 years were enrolled for the study with the purpose of assessing T2∗ values in healthy cartilage without any degenerative changes. The articular cartilage was assessed on two sections, one each through the medial and lateral compartments. The cartilage was segmented into 8 regions through the tibio-femoral and patella-femoral joints. Further post processing was done using multiple ROI placement to delineate ROI areas for calculation of full thickness and zonal (superficial and deep) T2∗ values. Thus, a total of 1200 ROI areas (50 volunteers, 8 segments, and 3 areas for each segment) were assessed. ResultsThe results revealed a superior bulk T2∗ value of 29.2 ± 3.6 ms from the posterior medial femoral cartilage and 26.1 ± 3.1 ms from the patellar region. Intermediate values were obtained from posterior lateral femoral cartilage, central femoral cartilage, and trochlea. The tibial plateau cartilage had the lowest values – 19.6 ± 2.6 ms for the medial tibial plateau and 20.6 ± 2.8 ms for lateral tibial plateau. The study demonstrated substantial regional physiological variation existing in the T2∗ values across various regions of the knee joint, which could be attributed to varying amounts of shearing forces across the joint. No significant differences were noted in bulk T2∗ values between the two genders, with only the trochlear segment revealing significantly increased values in males (p = 0.007). All the cartilage segments revealed significantly increased T2∗ values in the superficial zone as compared to the deep zone. ConclusionThere is a significant regional difference in the bulk T2∗ values of articular cartilage in a normal physiological state across various joint segments. A zonal gradient with increasing values from the deep to the superficial zone also exists. These findings can prove invaluable in assessing changes in T2∗ values occurring in diseased/degenerative cartilage.

CT and MRI Examination and Application Effect Analysis of Knee Meniscus and Articular Cartilage Injury

CT and MRI Examination and Application Effect Analysis of Knee Meniscus and Articular Cartilage Injury

Full domain surface distributions of micromechanical properties of articular cartilage structure obtained through indentation array

As a layered complicated porous elastic–plastic material, articular cartilages undertake the tasks of buffering stress, lubricating joint, and preventing wear. Nevertheless, the irregular articular cartilage shape indicates potential differences in properties at various regions. The lack of full domain surface micromechanical properties restricts the revelation of cartilage structure failure mechanism and impedes the design of biomimetic cartilage compatible with the actual working conditions. In the present work, the full domain knee articular cartilage surface was reasonably divided into microregions based on the approximate curvature principle. Through depth-sensing indentation array, the region-dependent differences in mechanical properties were revealed, and the hardness and Young's modulus distributions of full domain cartilage structure surface were experimentally obtained for the first time. The microstructure-property correlation was established and the microstructure-dependent load adaptability was also verified, as the region (concave side of condylar surface) with maximum hardness and Young's modulus exhibited a striped pattern with approximately consistent orientation, and the regions adjacent to the suprapatellar synovial bursa with lowest bearing capacity exhibited peeling collagen fibers.

Cartilage tissue engineering: From proinflammatory and anti‑inflammatory cytokines to osteoarthritis treatments (Review).

Osteoarthritis (OA), one of the most common joint diseases, is characterized by fibrosis, rhagadia, ulcers and attrition of articular cartilage due to a number of factors. The etiology of OA remains unclear, but its occurrence has been associated with age, obesity, inflammation, trauma and genetic factors. Inflammatory cytokines are crucial for the occurrence and progression of OA. The intra-articular proinflammatory and anti-inflammatory cytokines jointly maintain a dynamic balance, in accordance with the physiological metabolism of articular cartilage. However, dynamic imbalance between proinflammatory and anti-inflammatory cytokines can cause abnormal metabolism in knee articular cartilage, which leads to deformation, loss and abnormal regeneration, and ultimately destroys the normal structure of the knee joint. The ability of articular cartilage to self-repair once damaged is limited, due to its inability to obtain nutrients from blood vessels, nerves and lymphatic vessels, as well as limitations in the extracellular matrix. There are several disadvantages inherent to conventional repair methods, while cartilage tissue engineering (CTE), which combines proinflammatory and anti-inflammatory cytokines, offers a new therapeutic approach for OA. The aim of the present review was to examine the proinflammatory factors implicated in OA, including IL-1β, TNF-α, IL-6, IL-15, IL-17 and IL-18, as well as the key anti-inflammatory factors reducing OA-related articular damage, including IL-4, insulin-like growth factor and TGF-β. The predominance of proinflammatory over anti-inflammatory cytokine effects ultimately leads to the development of OA. CTE, which employs mesenchymal stem cells and scaffolding technology, may prevent OA by maintaining the homeostasis of pro- and anti-inflammatory factors.

Generation of hybrid tissue engineered construct through embedding autologous chondrocyte loaded platelet rich plasma/alginate based hydrogel in porous scaffold for cartilage regeneration

Over the past decades, various attempts have been made to develop suitable tissue-engineered constructs to repair or regenerate the damaged or diseased articular cartilage. In the present study, we embedded Platelet rich plasma (PRP)/Sodium Alginate (SA) based hydrogel in porous 3D scaffold of chitosan (CH)/chondroitin sulfate (CS)/silk fibroin (SF) to develop hybrid scaffold for cartilage tissue construct generation with abilities to support shape recovery potential, facilitate uniform cells distribution and mimic gel like cartilage tissue extracellular matrix.The developed hybrid matrix shows suitable pore size (55–261 μm), porosity (77 ± 4.3%) and compressive strength (0.13 ± 0.04 MPa) for cartilage tissue construct generation and its applications. The developed SA/PRP-based cartilage construct exhibits higher metabolic activity, glycosaminoglycan deposition, expression of collagen type II, and aggrecan in comparison to SA based cell-scaffold construct. In-vivo animal study was also performed to investigate the biocompatibility and cartilage tissue regeneration potential of the developed construct. The obtained gross analysis of knee sample, micro-computed tomography, and histological analysis suggest that implanted tissue construct possess the superior potential to regenerate hyaline cartilage defect of thickness around 1.10 ± 0.36 mm and integrate with surrounding tissue at the defect site. Thus, the proposed strategy for the development of cartilage tissue constructs might be beneficial for the repair of full-thickness knee articular cartilage defects.

Effects of different courses of moxibustion treatment on intestinal flora and inflammation of a rat model of knee osteoarthritis

ObjectiveThis study was done to determine the effects of different courses of moxibustion on a rat knee osteoarthritis (KOA) model, and explore the dose–effect relationship of moxibustion on KOA from the perspectives of intestinal flora and inflammatory factors. MethodsWistar rats were randomly divided into five groups: normal, model, moxibustion for 2 weeks, moxibustion for 4 weeks and moxibustion for 6 weeks groups (n = 5 each group). A KOA rat model was induced by monosodium iodoacetate, and moxibustion intervention was performed at the acupoints “Dubi” (ST35) and “Zusanli” (ST36), once every other day. Pathologic changes in the cartilage of rat knee joints were assessed after intervention, and fecal samples were subjected to 16S rRNA high-throughput sequencing for microbial diversity analysis. ResultsDamage to the knee articular cartilage was obvious in the model group, which also had increased levels of pro-inflammatory factors, decreased levels of anti-inflammatory factors, and intestinal flora disorders with decreased diversity. The degree of cartilage damage in the 4 and 6 weeks of moxibustion groups was significantly improved compared with the model group. The 4 and 6 weeks of moxibustion groups also demonstrated reduced levels of interleukin-1β and tumor necrosis factor-α and increased levels of interleukin-10 (P < 0.05). Both the abundance and diversity of the intestinal flora were increased, approaching those of the normal group. Abundances of probiotics Eubacterium coprostanoligenes group and Ruminococcaceae UCG-014 increased, while that of the pathogenic bacteria Lachnospiraceae NK4A136 group decreased (P < 0.05). Although the abundance of Lachnospiraceae NK4A136 group decreased in the 2 weeks of moxibustion group compared with the model group (P < 0.05), there was no statistically significant difference in serum inflammatory factors, flora species diversity or degree of pathological damage compared with the model group. ConclusionMoxibustion treatment led to significant improvements in the intestinal flora and inflammatory factors of rats with KOA. Moxibustion treatment of 4 and 6 weeks led to better outcomes than the 2-week course. Moxibustion for 4 and 6 weeks can regulate intestinal flora dysfunction with increased probiotics and reduced pathogenic bacteria, reduce pro-inflammatory factors and increase anti-inflammatory factors. No significant differences were seen between the effects of moxibustion for 4 weeks and 6 weeks.

Altered Expression of the Hedgehog Pathway Proteins BMP2, BMP4, SHH, and IHH Involved in Knee Cartilage Damage of Patients With Osteoarthritis and Kashin-Beck Disease

ObjectiveTo investigate the expression of Hedgehog (HH) signaling pathway proteins in knee articular cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA) patients.MethodsKnee articular cartilage samples were collected from normal (N), OA, and KBD adults (aged 38-60 years) and divided into 3 groups with 6 subjects in each group. The localization of the HH pathway proteins bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4), Sonic hedgehog (SHH), and Indian hedgehog (IHH) was observed with the microscope after immunohistochemical (IHC) staining. Positive staining cell rates of each proteins were compared.ResultsThe strongest stainings of all proteins were observed in the middle zones of all 3 groups. The positive staining rates of BMP4 and IHH were significantly lower in the OA and KBD groups than those in the N group in all 3 zones. The positive staining rates of BMP2 and SHH tend to be lower in the OA and KBD groups than those in the N group in the deep zone, while higher in the OA and KBD groups than those in the N group in superficial and middle zones.ConclusionsAltered expression of the HH pathway proteins BMP2, BMP4, SHH, and IHH was found in OA and KBD articular cartilage. There seemed to be a compensatory effect between SHH and IHH in cartilage damage. Further studies on the pathogenesis of OA and KBD may be carried out from these aspects in the future.

Treatment of Traumatic Cartilage Defects of Rabbit Knee Joint by Adipose Derived Stem Cells Combined with Kartogenin Hydroxyapatite Nano-Microsphere Complex.

Kartogenin (KGN) can effectively promote the differentiation of adipose derived stem cells (ADSCs) into chondrocytes. With the help of three-dimensional slow-release technology, nano-microspheres are generated and used for cartilage repair. First, KGN solution was prepared, which was dissolved in distilled water, and NaOH solution, HEPES buffer, sodium chloride particles, and hydroxyapatite (HA) solution were added to prepare KGN-HA gel solution containing KGN. ADSCs were isolated from the posterior iliac of four-week-old New Zealand rabbits. After 0.5 mL of rabbit second-generation ADSCs suspension was taken, 2 mL KGN-HA gel solution was added, and they were mixed well to obtain ADSCs/KGN-HA gel. After drying treatment, ADSCs/KGN-HA nanospheres were precipitated. In the experiment, the minimum inhibitory concentration (MIC) of Staphylococcus aureus (MIC) > 2 μg/mL in each group of KGN-HA gel solution was reached within 30 days. Group K3 had the highest KGN encapsulation rate and the largest cumulative release. The biological activity of ADSCs was good in the ADSCs/KGN-HA nanoparticle solution. After two weeks of incubation, the nanospheres were positive for type II collagen staining/toluidine blue staining, that was, chondrocyte phenotype. The rabbit knee articular cartilage defect model was established. The defect part was filled with ADSCs/KGN-HA gel, which was similar in color to the surrounding tissues. The two sides of the tissue section and the surrounding cartilage tissue healed well, and no carrier material remained. Moreover, the cells were round, with cartilage lacuna formed around them, and after the simple periosteum was covered and repaired, the surface was sunken. The cell structure changed, and the healing with the surroundings was poor. In summary, under the slow release of KGN, ADSCs/KGN-HA nanospheres made ADSCs maintain a good biological form, which grew and proliferated normally. The ADSCs/KGN-HA nanoparticles cultured in vitro had a good repair effect on the animal model of articular cartilage defects.

Cangxitongbi capsules protect the articular cartilage in the rat knee through the long non-coding RNA HOTAIR/p38MAPK pathway.

BackgroundKnee osteoarthritis (KOA) is a leading cause of chronic pain and disability, and as such, it poses a significant economic burden. Traditional Chinese medicine (TCM), as well as complementary and alternative medicine, can offer safe and effective treatments for KOA. Cangxitongbi (CXTB) capsule is a Chinese patented medicine for KOA treatment and has a remarkable curative effect. This article evaluated the effects and mechanisms of CXTB in protecting joint cartilage in vivo.MethodsThe KOA model was constructed in rats using the modified Hulth method. CXTB (35 mg/kg) was administered intragastrically for 4 weeks. Hematoxylin and eosin (HE) staining of the knee articular were performed to evaluate the efficiency of CXTB. Western blot analysis, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA) were used to investigate the protective mechanisms of CXTB in joint cartilage.ResultsCXTB effectively improved the morphological structure of the cartilage and bone in the knee joint by enhancing autophagy and regulating the expression of related protease and inflammatory factors. Furthermore, CXTB downregulated the expression of the long non-coding RNA (lncRNA) Hox transcript antisense intergenic RNA (HOTAIR) and inhibited the activation of the p38MAPK pathway. Conversely, overexpression of lncRNA HOTAIR suppressed the protective effects of CXTB on the knee joint.ConclusionsCXTB capsules can protect the knee articular cartilage in rats through the lncRNA HOTAIR/p38MAPK pathway.