Cartilage Protection Research Articles

Platelet Rich Plasma in the Repair of Articular Cartilage Injury: A Narrative Review.

ObjectiveThis paper reviews the research of platelet-rich plasma (PRP) in articular cartilage injury repair, to assess the mechanism, utilization, and efficacy of PRP in the treatment of articular cartilage injury, hoping to provide a theoretical basis for the clinical application of PRP in the future.Materials and MethodsA comprehensive database search on PRP applications in cartilage repair was performed. Among them, the retrieval time range of PRP in clinical trials of repairing knee cartilage injury was from January 1, 2021 to January 1, 2022. Non-clinical trials and studies unrelated to cartilage injury were excluded.ResultPRP can affect inflammation, angiogenesis, cartilage protection, and cellular proliferation and differentiation after articular cartilage injury through different pathways. In all, 13 clinical trials were included in the analysis.ConclusionPRP is an emergent therapeutic approach in tissue engineering. Most studies reported that PRP has a positive effect on cartilage injury, improving the joint function, meanwhile there is a lack of standardized standards. The technology of PRP in the repair and treatment of articular cartilage injury is worthy of further research.

Paper 01: ACL Reconstructed Knees Had Significantly Higher MR T1ρ and T2 Values in Cartilage but not in Meniscus Compared to Contralateral Knees at 10 Years after ACL Reconstruction

Paper 01: ACL Reconstructed Knees Had Significantly Higher MR T1ρ and T2 Values in Cartilage but not in Meniscus Compared to Contralateral Knees at 10 Years after ACL Reconstruction

Lateral meniscus allograft transplantation without bone plugs: technique and outcomes.

Once considered a non-fundamental structure, the menisci are now known to provide several functions within the knee, including protection of articular cartilage, load-bearing, shock absorption, joint stability, joint lubrification and joint congruity functions. Meniscal tears are one of the most common lesions in knee orthopedics, and partial or total meniscectomies are commonly performed procedures in orthopedic surgery. Despite meniscectomy is well recognized to lead improvement in clinical outcomes, it has been related to early onset knee osteoarthritis and joint degeneration which are associated with pain and functional limitations. Meniscal allograft transplantation has become a viable option for patients under 55 years old that have undergone total or near total meniscectomy and are in a painful state. This procedure can be performed using bone plugs or without bone plugs. In the bone plugs free technique allograft will be presented as a lateral meniscus with a portion of tibial plateau and is then introduced into the joint through an arthroscopic portal and fixed to the capsule with all-inside stitches. The most important aspect required to obtain good clinical results are graft size, anatomic placement and fixation, because extrusion is the most common complication related to meniscal transplantation. Although a lack of long-term follow-up (FU) studies, it has been demonstrated that lateral meniscus transplantation without bone plugs is a minimal invasive surgical procedure that improves the knee function, increases patient physical activity and reduces pain.

Mitochonic Acid-5 Inhibits Reactive Oxygen Species Production and Improves Human Chondrocyte Survival by Upregulating SIRT3-Mediated, Parkin-dependent Mitophagy.

Mitochondrial dysfunction is related to the pathogenesis of osteoarthritis (OA); however, there are no effective drugs to treat OA for maintaining mitochondrial homeostasis. Studies have shown that mitochonic acid-5 (MA-5) has a protective effect against mitochondrial damage and plays a role in mitophagy. However, it is not clear whether MA-5 has a beneficial effect on inflammatory articular cartilage. Here, human OA cartilage was obtained from patients undergoing total joint replacement. Interleukin-1β (IL-1β) was used to stimulate chondrocytes and induce inflammatory injury. Cell Counting Kit-8, TUNEL, and flow cytometry assays were used to assess apoptosis. Gene expression was examined using quantitative reverse transcription-polymerase chain reaction. Mitochondrial function was evaluated using immunoblotting, mitochondrial membrane potential assay, JC-1 staining, and immunofluorescence analysis. Mitophagy was detected using immunoblotting and immunofluorescence. 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP), a specific inhibitor of Sirtuin 3 (SIRT3), was used to block the SIRT3/Parkin pathway. Mitophagy in the cartilage sections was evaluated via immunohistochemistry. IL-1β was found to induce chondrocyte apoptosis by inhibiting SIRT3 expression and mitophagy. In addition, inflammatory damage reduced the mitochondrial membrane potential and promoted the production of intracellular reactive oxygen species (ROS), leading to increased mitochondrial division, mitochondrial fusion inhibition, and the consequent mitochondrial damage. In contrast, the MA-5 treatment inhibited excessive ROS production by upregulating mitophagy, maintaining the mitochondrial membrane potential, and reducing mitochondrial apoptosis. After chemically blocking SIRT3 with 3-TYP, Parkin-related mitophagy was also inhibited, an effect that was prevented by pretreatment of the chondrocytes with MA-5, thereby suggesting that SIRT3 is upstream of Parkin. Overall, MA-5 was found to enhance the activity of SIRT3, promote Parkin-dependent mitophagy, eliminate depolarized/damaged mitochondria in chondrocytes, and protect cartilage cells. In conclusion, MA-5 inhibits IL-1β-induced oxidative stress and protects chondrocytes by upregulating the SIRT3/Parkin-related autophagy signaling pathway.

Lactobacillus acidophilus Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model.

To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA by partial medial meniscectomy (PMM). Pain was assessed by von Frey filament and hot plate testing. Joint pathology and pain markers were comprehensively analyzed in knee joints, spinal cords, dorsal root ganglia and distal colon by Safranin O/fast green staining, immunofluorescence microscopy and RT-qPCR. LA acutely reduced inflammatory knee joint pain and prevented further OA progression. The therapeutic efficacy of LA was supported by a significant reduction of cartilage-degrading enzymes, pain markers and inflammatory factors in the tissues we examined. This finding suggests a likely clinical effect of LA on OA. The effect of LA treatment on the fecal microbiome was assessed by 16S rRNA gene amplicon sequencing analysis. LA significantly altered the fecal microbiota compared to vehicle-treated mice (PERMANOVA p < 0.009). Our pre-clinical OA animal model revealed significant OA disease modifying effects of LA as reflected by rapid joint pain reduction, cartilage protection, and reversal of dysbiosis. Our findings suggest that LA treatment has beneficial systemic effects that can potentially be developed as a safe OA disease-modifying drug (OADMD).

Multifunctional injectable hydrogel for effective promotion of cartilage regeneration and protection against osteoarthritis: combined chondroinductive, antioxidative and anti-inflammatory strategy

ABSTRACT The regeneration of the articular cartilage defects is characterized by the improvement in the quality of the repaired tissue and the reduction in the potential development of perifocal osteoarthritis (OA). Usually, the injection of dexamethasone (Dex) in the OA joints slows down the progression of inflammation and relieves pain. However, the anti-inflammatory Dex injected in the joint cavity is rapidly cleared, leading to a poor therapeutic effect. Multifunctional hydrogels with simultaneous chondrogenic differentiation, antioxidative, and anti-inflammatory capacities may represent a promising solution. Therefore, in this work, a novel injectable hydrogel based on double cross-linking of Schiff base bonds and coordination of catechol-Fe was developed. The obtained hydrogel (Gel-DA/DOHA/DMON@Dex@Fe) possessed molding performance in situ, excellent mechanical strength, controllable biodegradability, the on-demand release of the drug, and biocompatibility. The hydrogel system stimulated the HIF-1α signaling pathway and suppressed inflammation thanks to the introduction of DMON@Fe, consequently facilitating chondrogenic differentiation. The synergistic anti-inflammatory effect together with the induction of chondrogenesis by Dex-loaded Gel-DA/DOHA/DMON@Fe hydrogel allowed the promotion of cartilage repair, as demonstrated by in vivo experiments. Hence, the proposed multifunctional scaffold provides a promising advancement in articular cartilage tissue engineering and may have great prospects in the prevention of OA.

Immunoregulation and anti-metalloproteinase bioactive injectable polysalicylate matrixgel for efficiently treating osteoarthritis.

Current treatments of osteoarthritis, such as oral medication and intra-articular injections, only provided temporary relief from pain and achieved limited advance in inhibiting progression. The development of new treatments is hindered by the complicated and unclear pathological mechanisms. Oxidative stress and immune inflammation are believed to be the important factors in the induction and progression of osteoarthritis. Herein, this work presents a bioactive material strategy to treat osteoarthritis, based on the FPSOH matrixgel with robust anti-inflammatory activity through inhibiting the oxidative stress and nuclear factor kappa B signaling, preventing the metalloproteinase, as well as inducing M2 polarization of macrophage, thereby providing immune regulation of synovial macrophages and suppressing the progression of synovitis and osteoarthritis. In vivo experiments demonstrated that FPSOH hydrogel can prevent papain-induced osteoarthritis and its progression, and provide dual protection for cartilage and synovium, as compared with commercial sodium hyaluronate.

Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis

Damaged hyaline cartilage has no capacity for self-healing, making osteoarthritis (OA) “difficult-to-treat”. Cartilage destruction is central to OA patho-etiology and is mediated by matrix degrading enzymes. Here we report decreased expression of miR-17 in osteoarthritic chondrocytes and its deficiency contributes to OA progression. Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5, effectively prevented OA by simultaneously targeting pathological catabolic factors including matrix metallopeptidase-3/13 (MMP3/13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2). Single-cell RNA sequencing of hyaline cartilage revealed two distinct superficial chondrocyte populations (C1/C2). C1 expressed physiological catabolic factors including MMP2, and C2 carries synovial features, together with C3 in the middle zone. MiR-17 is highly expressed in both superficial and middle chondrocytes under physiological conditions, and maintains the physiological catabolic and anabolic balance potentially by restricting HIF-1α signaling. Together, this study identified dual functions of miR-17 in maintaining cartilage homeostasis and prevention of OA.

Nanoparticle functionalization with genetically-engineered mesenchymal stem cell membrane for targeted drug delivery and enhanced cartilage protection.

Articular cartilage encounters structural damage and tissue degeneration during osteoarthritis. It is of great significance to effectively deliver the therapeutic drug to the location of the cartilage lesion. Nanoparticle-based biomimetic systems provide an important solution for drug delivery, but they still lack the active targeting capability. Although some physical and chemical modifications could decrease non-specific interactions to some extent, a specific bio-interaction for active targeting is still required for many biomedical purposes. In this study, we proposed genetically-engineered mesenchymal stem cell membrane-derived nanoparticles with the active targeting capability. BMSCs were engineered for the high expression of CXCR4 to actively migrate to the injured locations, and cell membrane of the engineered BMSCs was isolated and camouflaged to fluorescent nanoparticles. The modified nanoparticles that loaded with the therapeutic drug were incubated with IL-1β-induced injured articular chondrocytes and cartilage. The results invisibly demonstrated that these engineered nanoparticles could increase both cellular uptake and penetration depth in the target cells and tissues under inflammatory microenvironments to protect the injured cartilage. Therefore, this genetically-modified nanoparticle functionalization strategy is expected to provide evidence for active targeting in the tissue injury treatment.

The immediate meniscal allograft transplantation achieved better chondroprotection and less meniscus degeneration than the conventional delayed transplantation in the long-term.

The purpose of this study was to compare the long-term clinical and radiological outcomes between the immediate and delayed meniscus allograft transplantation (MAT). Nine menisci were transplanted immediately after total meniscectomy (immediate group, IM), and 10 menisci were delayed transplanted in patients with the median of 35months (range 9-92months) after total meniscectomy (delayed group, DE). Patient's subjective clinical outcomes including VAS, IKDC, Lysholm and Tegner scores as well as muscle strength measures were compared. Joint degeneration was evaluated by both radiographs to assess joint space width narrowing, Kellegren-Lawrence (KL) grade and MRI with T2 mapping sequences to quantitatively analyze both cartilage and meniscal allograft degeneration. The median follow-up time was 10.8years (range 10-14years). The IKDC (IM vs DE, 89.8 vs 80.9, n.s.) and Lysholm scores (IM vs DE, 87.7 vs 78.0, n.s.) were close in two groups, while the IM group showed slightly lower VAS (IM vs DE, 0.2 vs 1.5, p = 0.031), higher Tegner score (IM vs DE, 7 vs 3.5 p = 0.021) and better quadriceps muscle strength. The IM group had less joint space narrowing (IM vs DE, 0.35mm vs 0.71mm, n.s.), less KL grade progression (IM vs DE, 0.6 vs 1.7, p = 0.041) on radiographs and less chondral lesions development on MRIs (Cartilage Degeneration Index, IM vs DE, 252 vs 2038, p = 0.025). All meniscal grafts exhibited degeneration by showing grade 3 signal on MRI, and 4 (4/9) in the IM group and 8 (8/10) cases in the DE group. The T2 value of cartilage and meniscal allograft in the IM group was close to that of the healthy control and was significantly lower than that of the DE group. Compared to the conventional delayed MAT, the immediate MAT achieved better cartilage and meniscus protection in the long-term, while its superiority in patient-reported outcomes was limited. IV.

Demineralized Cortical Bone Matrix Augmented With Peripheral Blood-Derived Mesenchymal Stem Cells for Rabbit Medial Meniscal Reconstruction.

Tissue engineering is a promising treatment strategy for meniscal regeneration after meniscal injury. However, existing scaffold materials and seed cells still have many disadvantages. The objective of the present study is to explore the feasibility of peripheral blood-derived mesenchymal stem cells (PBMSCs) augmented with demineralized cortical bone matrix (DCBM) pretreated with TGF-β3 as a tissue-engineered meniscus graft and the repair effect. PBMSCs were collected from rabbit peripheral blood and subjected to three-lineage differentiation and flow cytometry identification. DCBM was prepared by decalcification, decellularization, and cross-linking rabbit cortical bone. Various characteristics such as biomechanical properties, histological characteristics, microstructure and DNA content were characterized. The cytotoxicity and the effects of DCBM on the adhesion and migration of PBMSCs were evaluated separately. The meniscus-forming ability of PBMSCs/DCBM complex in vitro induced by TGF-β3 was also evaluated at the molecular and genetic levels, respectively. Eventually, the present study evaluated the repair effect and cartilage protection effect of PBMSCs/DCBM as a meniscal graft in a rabbit model of medial meniscal reconstruction in 3 and 6 months. The results showed PBMSCs positively express CD29 and CD44, negatively express CD34 and CD45, and have three-lineage differentiation ability, thus can be used as tissue engineering meniscus seed cells. After the sample procedure, the cell and DNA contents of DCBM decreased, the tensile modulus did not decrease significantly, and the DCBM had a pore structure and no obvious cytotoxicity. PBMSCs could adhere and grow on the scaffold. Under induction of TGF-β3, PBMSCs/DCBM composites expressed glycosaminoglycan (GAG), and the related gene expression also increased. The results of the in vivo experiments that the PBMSCs/DCBM group had a better repair effect than the DCBM group and the control group at both 12 and 24 weeks, and the protective effect on cartilage was also better. Therefore, the application of DCBM augmented with PBMSCs for meniscus injury treatment is a preferred option for tissue-engineered meniscus.

HDAC6 regulates NF-\u03baB signalling to control chondrocyte IL-1-induced MMP and inflammatory gene expression

Elevated pro-inflammatory signalling coupled with catabolic metalloproteinase expression is a common feature of arthritis, leading to cartilage damage, deterioration of the joint architecture and the associated pain and immobility. Countering these processes, histone deacetylase inhibitors (HDACi) have been shown to suppress matrix metalloproteinase (MMP) expression, block cytokine-induced signalling and reduce the cartilage degradation in animal models of the arthritis. In order to establish which specific HDACs account for these chondro-protective effects an HDAC1-11 RNAi screen was performed. HDAC6 was required for both the interleukin (IL)-1 induction of MMP expression and pro-inflammatory interleukin expression in chondrocytes, implicating an effect on NF-κB signalling. Depletion of HDAC6 post-transcriptionally up-regulated inhibitor of κB (IκB), prevented the nuclear translocation of NF-κB subunits and down-regulated NF-κB reporter activation. The pharmacological inhibition of HDAC6 reduced MMP expression in chondrocytes and cartilage collagen release. This work highlights the important role of HDAC6 in pro-inflammatory signalling and metalloproteinase gene expression, and identifies a part for HDAC6 in the NF-κB signalling pathway. By confirming the protection of cartilage this work supports the inhibition of HDAC6 as a possible therapeutic strategy in arthritis.

Characterization of Microfragmented Adipose Tissue Architecture, Mesenchymal Stromal Cell Content and Release of Paracrine Mediators.

The use of microfragmented adipose tissue (µFAT) for the treatment of musculoskeletal disorders, especially osteoarthritis (OA), is gaining popularity, following positive results reported in recent case series and clinical trials. Although these outcomes were postulated to rely on paracrine signals, to date, a thorough fingerprint of released molecules is largely missing. The purpose of this study was to first characterize both structure and cell content of unprocessed lipoaspirate (LA) and µFAT, and further identify and frame the array of signaling factors in the context of OA disease, by means of high throughput qRT-PCR for extracellular-vesicle (EV) embedded miRNAs and proteomics for tissue and secreted factors. Cell count showed reduction of blood cells in µFAT, confirmed by histological and flow cytometry analyses, that also showed a conserved presence of structural, endothelial and stromal components and pericytes. In the secretome, 376 and 381 EV-miRNAs in LA and µFAT, respectively, were identified. In particular, most abundant and µFAT upregulated EV-miRNAs were mainly recapitulating those already reported as ASC-EVs-specific, with crucial roles in cartilage protection and M2 macrophage polarization, while only a scarce presence of those related to blood cells emerged. Furthermore, secretome proteomic analysis revealed reduction in µFAT of acute phase factors driving OA progression. Taken together, these results suggest that processing of LA into µFAT allows for removal of blood elements and maintenance of tissue structure and stromal cell populations, and possibly the increase of OA-protective molecular features. Thus, microfragmentation represents a safe and efficient method for the application of adipose tissue properties in the frame of musculoskeletal disorders.

Intra-articular injectable hydroxypropyl chitin/hyaluronic acid hydrogel as bio-lubricant to attenuate osteoarthritis progression

Osteoarthritis is a chronic degenerative joint disease and its signs of progress mainly attribute to the significant increase of joint friction and the destruction of articular cartilage. Combined cartilage repair and joint lubrication may be a feasible strategy for the treatment of osteoarthritis. In this study, the hydroxypropyl chitin (HPCH)/hyaluronic acid (HA) hydrogel, prepared by physical mixing of HA and HPCH, was designed to be a new bio-lubricant and a chondroprotective agent for osteoarthritis treatment. HA release in HPCH/HA hydrogel was more durable and stable and in vitro experiments showed that HPCH/HA hydrogel could promote the synthesis of the extracellular matrix of chondrocytes. Additionally, HPCH/HA hydrogel could delay the progression of osteoarthritis in DMM-induced osteoarthritis mouse model. To sum up, HPCH/HA hydrogel developed herein can achieve the dual function of well lubrication of joints and protection of cartilage and has the clinical potential as synergetic treatment of osteoarthritis.

Preparation of epigallocatechin gallate decorated Au-Ag nano-heterostructures as NIR-sensitive nano-enzymes for the treatment of osteoarthritis through mitochondrial repair and cartilage protection

Osteoarthritis (OA), a widespread degenerative disease characterized by cartilage destruction, has emerged as a public health challenge in the current aging society. In addition to applied steroids and surgery, near-infrared (NIR) sensitive nano-enzyme for the treatment of osteoarthritis through mitochondrial repair and cartilage protection is attractive and promising. In this study, a NIR sensitive multifunctional heterostructure (EGCG (Epigallocatechin gallate) decorated Au-Ag nano-jars (E@Au-Ag)) was introduced as an enzyme-sensitive active nanoplatform for the treatment of osteoarthritis. Molecular biology results indicated that E@Au-Ag possesses intrinsic properties of anti-oxidative stress and was able to reduce the apoptosis rate of chondrocytes by 83.3%. The area of the intra-articular joint cavity injected with E@Au-Ag can be elevated to 46.6 °C under NIR to promote the release of EGCG further to induce cartilage regeneration. X-ray radiography and section staining showed that E@Au-Ag reduced cartilage damage and decreased OARSI scores by approximately 52% after 8 weeks of treatment in a surgically induced OA model. The results demonstrated that this multifunctional enzyme-like nanoplatform with a synergistic NIR sensitive property to facilitate cartilage migration and regeneration repair provides a promising OA treatment strategy. Statement of significance1. NIR-sensitive nano-enzyme is gaining much attention in the field of biomedical materials.2. EGCG decorated Au-Ag nano-heterostructures were utilized as NIR-sensitive nano-enzymes for the treatment of osteoarthritis through mitochondrial repair and cartilage protection.3. The obtained multifunctional Au-Ag nano-heterostructures are promising for osteoarthritis treatment.

Dopamine-conjugated hyaluronic acid delivered via intra-articular injection provides articular cartilage lubrication and protection

Due to its high molecular weight and viscosity, hyaluronic acid (HA) is widely used for viscosupplementation to provide joint pain relief in osteoarthritis. However, this benefit is temporary due to poor adhesion of HA on articular surfaces. In this study, we therefore conjugated HA with dopamine to form HADN, which made the HA adhesive while retaining its viscosity enhancement capacity. We hypothesized that HADN could enhance cartilage lubrication through adsorption onto the exposed collagen type II network and repair the lamina splendens. HADN was synthesized by carbodiimide chemistry between hyaluronic acid and dopamine. Analysis of Magnetic Resonance (NMR) and Ultraviolet spectrophotometry (Uv–vis) showed that HADN was successfully synthesized. Adsorption of HADN on collagen was demonstrated using Quartz crystal microbalance with dissipation (QCM-D). Ex vivo tribological tests including measurement of coefficient of friction (COF), dynamic creep, in stance (40 N) and swing (4 N) phases of gait cycle indicated adequate protection of cartilage by HADN with higher lubrication compared to HA alone. HADN solution at the cartilage-glass sliding interface not only retains the same viscosity as HA and provides fluid film lubrication, but also ensures better boundary lubrication through adsorption. To confirm the cartilage surface protection of HADN, we visualized cartilage wear using optical coherence tomography (OCT) and atomic force microscopy (AFM).

A biomechanical comparison between cement packing combined with extra fixation and three-dimensional printed strut-type prosthetic reconstruction for giant cell tumor of bone in distal femur

BackgroundThe most common reconstruction method for bone defects caused by giant cell tumor of bone (GCTB) is cement packing combined with subchondral bone grafting and extra fixation. However, this method has several limitations involving bone cement and bone graft, which may lead to poor prognosis and joint function. A titanium-based 3D-printed strut-type prosthesis, featured with excellent biocompatibility and osseointegration ability, was developed for this bone defect in our institution. The goal of this study is to comparatively analyze the biomechanical performance of reconstruction methods aimed at the identification of better operative strategy.MethodsFour different 3D finite element models were created. Model #1: Normal femur; Model #2: Femur with tumorous cavity bone defects in the distal femur; Model #3: Cavity bone defects reconstructed by cement packing combined with subchondral bone grafting and extra fixation; Model #4: Cavity bone defects reconstructed by 3D-printed strut-type prosthesis combined with subchondral bone grafting. The femoral muscle multiple forces were applied to analyze the mechanical difference among these models by finite element analysis.ResultsOptimal stress and displacement distribution were observed in the normal femur. Both reconstruction methods could provide good initial stability and mechanical support. Stress distributed unevenly on the femur repaired by cement packing combined with subchondral bone grafting and extra fixation, and obvious stress concentration was found around the articular surface of this femur. However, the femur repaired by 3D-printed strut-type prosthetic reconstruction showed better performance both in displacement and stress distribution, particularly in terms of the protection of articular surface and subchondral bone.Conclusions3D-printed strut-type prosthesis is outstanding in precise shape matching and better osseointegration. Compared to cement packing and extra fixation, it can provide the almost same support and fixation stiffness, but better biomechanical performance and protection of subchondral bone and articular cartilage. Therefore, 3D-printed strut-type prosthetic reconstruction combined with subchondral bone grafting may be evaluated as an alternative for the treatment of GCTBs in distal femur.

Curcumin primed ADMSCs derived small extracellular vesicle exert enhanced protective effects on osteoarthritis by inhibiting oxidative stress and chondrocyte apoptosis

Osteoarthritis (OA) is a common joint disease caused by progressive articular cartilage degeneration and destruction. Currently, there are no disease-modifying agents officially approved for OA patients. In this study, curcumin was loaded into adipose tissue-derived mesenchymal stem cells (ADMSCs)-derived small extracellular vesicle (ADMSCs-sEV) to synergistically exert chondro-protective effects in vitro and in vivo. We found curcumin primed ADMSCs derived sEV (sEV-CUR) exhibited an enhanced protective effect compared with free curcumin and ADMSCs-sEV in TBHP-induced chondrocytes. Moreover, our study demonstrated sEV-CUR more effectively down-regulated TBHP-induced oxidative stress and chondrocyte apoptosis in vitro. In OA mice model, our results indicated that sEV-CUR showed an improved cartilage protection, as biweekly intra-articular injection of sEV-CUR more efficaciously alleviated oxidative stress and chondrocyte apoptosis in OA cartilage. Overall, our findings showed sEV-CUR exhibited enhanced chondro-protective effects and holds great potential on the recovery of articular cartilage loss and destruction in OA patients.Graphical

Paeonol inhibits inflammatory response and protects chondrocytes by upregulating sirtuin 1.

Paeonol is the bioactive component in Paeonia lactiflora Pall., Cynanchum paniculatum and Paeonia × suffruticosa Andr. Paeonol has been previously demonstrated to inhibit the release of tumor necrosis factor α (TNF-α) and interluekin 6 (IL-6) in chondrocytes. Sirtuin 1 (SIRT1) is downregulated in degraded cartilage and paeonol could induce nuclear accumulation of SIRT1. Therefore, the present study aims to investigate the possible role of paeonol in chondrocyte inflammation and cartilage protection in osteoarthritis (OA) as well as its regulation of SIRT1. Primary chondrocytes from rat knee joints were transfected with short hairpin (sh) - SIRT1 and (or) paeonol prior to IL-1β exposure, and then inflammatory response, apoptosis, and extracellular matrix (ECM) degradation in the cells were evaluated concurrent with the activation of the nuclear factor κβ (NF-κβ) signaling pathway. Increased levels of TNF-α, IL-17, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 along with decreased tissue inhibitor of metalloproteinases 1 and type II collagen levels were found in IL-1β-stimulated chondrocytes. Chondrocyte apoptosis was elevated and the NF-κβ signaling pathway was activated in response to IL-1β treatment. Paeonol enhanced SIRT1 expression to inactivate the NF-κβ signaling pathway, thereby ameliorating inflammatory cytokine secretion, ECM degradation, and chondrocyte apoptosis. In conclusion, the results of the present study confirm the potential of paeonol as a candidate OA drug.

Comparison of Acetabular Labral Reconstruction With 7-mm Tibialis Anterior Allograft and 5-mm Iliotibial Band Autograft at Minimum 2-Year Follow-up

Background: Labral reconstruction has been described as a treatment option for irreparable labral tear. Labral graft size ranges from 5 to 7 mm2 for reconstruction. A thicker labral graft could support mechanical stability and protect cartilage better. No study has compared the effect of graft thickness on clinical outcomes. Purpose/Hypothesis: The purpose of this study was to compare patient-reported outcomes between hips reconstructed with an autologous iliotibial band (AUITB; 5 mm2) graft and with an allogenic tibialis anterior (ALTA; 7 mm2) tendon graft. Our hypothesis was that hips reconstructed with a thicker allograft (7 mm2) would have better clinical outcomes than those with a smaller autograft (5 mm2). Study Design: Cohort study; Level of evidence, 2. Methods: A total of 42 patients (aged 21 to 54 years) underwent arthroscopic hip segmental labral reconstruction during the study period of January 2016 to November 2018. Twenty patients had reconstruction with AUITB grafts (5 mm2) and 22 with ALTA grafts (7 mm2). Both groups had minimum 2 year follow-up. Patients were evaluated with patient-related outcome scores: modified Harris Hip Score, Nonarthritic Hip Score, and Hip Outcome Score–Sports Specific. Pain evaluation was performed using a visual analog scale. Results: There were significant differences in all studied variables when comparing pre- and postoperative scores. Yet, there were no differences in terms of patient-related outcome scores between the groups postoperatively. Postoperative visual analog scale scores averaged 2.1 for the AUITB group vs 1.9 for the ALTA group (P = .89); modified Harris Hip Score, 82.7 vs 83.3 (P = .77); Nonarthritic Hip Score, 81.1 vs 82.2 (P = .81); and Hip Outcome Score–Sports Specific, 81.6 vs 82.5 (P = .67). Conclusion: No differences were found in terms of clinical outcomes between the 7-mm2 ALTA graft and the 5-mm2 AUITB graft. Both graft types and thicknesses might be considered comparable choices for primary reconstruction. Although a thicker-graft labral reconstruction seemed to have more ability to cover joint surface, clinical results did not show any superiority of a thicker graft whether it is autologous or allogenic.