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Journal of Cell Communication and... Jun 2024Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1...
Adipocyte enhancer binding protein 1 knockdown alleviates osteoarthritis through inhibiting NF-κB signaling pathway-mediated inflammation and extracellular matrix degradation.
Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients ( = 20) compared to their normal controls ( = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1β treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1β-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.
PubMed: 38946719
DOI: 10.1002/ccs3.12022 -
Tissue Engineering. Part C, Methods Jul 2024Current tissue engineering methods utilize chondrocytes primarily from costal or articular sources. Despite the robust mechanical properties of neocartilages sourced...
Current tissue engineering methods utilize chondrocytes primarily from costal or articular sources. Despite the robust mechanical properties of neocartilages sourced from these cells, the lack of elasticity and invasiveness of cell collection from these sources negatively impact clinical translation. These limitations invited the exploration of naturally elastic auricular cartilage as an alternative cell source. This study aimed to determine if auricular chondrocytes can be used for tissue engineering scaffold-free neocartilage constructs and assess their biomechanical properties. Neocartilages were successfully generated from a small quantity of primary neonatal auricular chondrocytes of three minipig donors (N=3). Neocartilage constructs had Instantaneous moduli (Ei) of 200.5 kPa ± 43.34 and 471.9 kPa ± 92.8 at 10% and 20% strain, respectively. TE constructs' relaxation moduli (Er) were 36.99 kPa ± 6.47 Er and 110.3 kPa ± 16.99 at 10% and 20% strain, respectively. The Young's modulus was 2.0 MPa ± 0.63, and the ultimate tensile strength (UTS) was 0.619 MPa ± 0.177. Auricular chondrocyte-derived neocartilages contained 0.144 ug ± 0.011 collagen, 0.185 ug ± 0.002 glycosaminoglycans per ug dry weight, and 1.7e-3 ug elastin per ug dry weight. In conclusion, this study shows that auricular chondrocytes can be used as a reliable and easily accessible cell source for tissue engineering of biomimetic and mechanically robust elastic neocartilage implants.
PubMed: 38946581
DOI: 10.1089/ten.TEC.2024.0106 -
Autoimmunity Dec 2024Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic...
BACKGROUND
Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.
OBJECTIVE
This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms.
METHODS
An injury cell model was established by treating chondrocytes with IL-1β. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 .
RESULTS
Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2.
CONCLUSION
Osteocyte-derived exosomal DLX2 alleviated IL-1β-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.
Topics: Exosomes; Animals; Osteoarthritis; Mice; Transcription Factors; Homeodomain Proteins; Osteocytes; Wnt Signaling Pathway; Chondrocytes; Disease Models, Animal; Humans; Interleukin-1beta; Cartilage, Articular; Apoptosis; Cartilage; Male; Cell Movement; Cell Survival
PubMed: 38946534
DOI: 10.1080/08916934.2024.2364686 -
European Review For Medical and... Jun 2024This study investigates the biomechanical effects of graft width and chondrolabral junction (CLJ) preservation on the labral suction seal in a bovine hip model and aims...
OBJECTIVE
This study investigates the biomechanical effects of graft width and chondrolabral junction (CLJ) preservation on the labral suction seal in a bovine hip model and aims to validate this model as a practical alternative for hip biomechanical research by comparing it with human cadaver studies.
MATERIALS AND METHODS
Twenty hips from two-year-old male bovines were divided into two main groups: CLJ preserved (CLJ+) and CLJ excised (CLJ-). These groups were further divided into eight subgroups: Group 1 with an intact labrum; Group 2 with labrum excision preserving CLJ; Groups 3 and 4 with labral reconstruction on preserved CLJ using 4.5 mm and 9 mm grafts, respectively; Group 5 with a labral tear at 12 to 3 o'clock position without CLJ preservation; Group 6 with complete labrum excision without CLJ preservation; and Groups 7 and 8 with labral reconstruction on excised CLJ using 4.5 mm and 9 mm grafts. Mechanical tests measuring compression and distraction forces were conducted, recording force-displacement values.
RESULTS
Both CLJ+ and CLJ- groups showed that labrum excision resulted in the lowest distraction forces, emphasizing labral integrity. Notably, reconstruction with 9 mm grafts improved distraction forces more than 4.5 mm grafts (p<0.001). The change in distraction forces from intact to excised stages was nearly significant between CLJ+ and CLJ- groups (Δ Intact-excised: CLJ+ vs. CLJ-: 92 N vs. 105 N, p=0.08). Distraction forces were measured at 206±27 Newtons in the CLJ preserved group and 186±24 Newtons in the resected group.
CONCLUSIONS
This study demonstrates that increasing the width of the graft, despite being approximately half and a quarter of the native labrum's size, significantly enhances the distraction force in labral reconstruction within a bovine hip model. This improvement is more pronounced than the effects of preserving the CLJ, highlighting the critical role of graft size in maintaining the biomechanical integrity of the labral suction seal.
Topics: Animals; Cattle; Male; Biomechanical Phenomena; Hip Joint; Cartilage, Articular; Humans; Models, Animal
PubMed: 38946380
DOI: 10.26355/eurrev_202406_36459 -
International Journal of Biological... Jun 2024Cartilage repair and regeneration have become a global issue that millions of patients from all over the world need surgical intervention to repair the articular... (Review)
Review
Cartilage repair and regeneration have become a global issue that millions of patients from all over the world need surgical intervention to repair the articular cartilage annually due to the limited self-healing capability of the cartilage tissues. Cartilage tissue engineering has gained significant attention in cartilage repair and regeneration by integration of the chondrocytes (or stem cells) and the artificial scaffolds. Recently, polysaccharide-protein based scaffolds have demonstrated unique and promising mechanical and biological properties as the artificial extracellular matrix of natural cartilage. In this review, we summarize the modification methods for polysaccharides and proteins. The preparation strategies for the polysaccharide-protein based hydrogel scaffolds are presented. We discuss the mechanical, physical and biological properties of the polysaccharide-protein based scaffolds. Potential clinical translation and challenges on the artificial scaffolds are also discussed.
PubMed: 38944089
DOI: 10.1016/j.ijbiomac.2024.133495 -
Rheumatic Diseases Clinics of North... Aug 2024Osteoarthritis (OA) causes a massive disease burden with a global prevalence of nearly 23% in 2020 and an unmet need for adequate treatment, given a lack of... (Review)
Review
Osteoarthritis (OA) causes a massive disease burden with a global prevalence of nearly 23% in 2020 and an unmet need for adequate treatment, given a lack of disease-modifying drugs (DMOADs). The author reviews the prospects of active DMOAD candidates in the phase 2/3 clinical trials of drug development pipeline based on key OA pathogenetic mechanisms directed to inflammation-driven, bone-driven, and cartilage-driven endotypes. The challenges and possible research opportunities are stated in terms of the formulation of a research question known as the PICO approach: (1) population, (2) interventions, (3) comparison or placebo, and (4) outcomes.
Topics: Humans; Osteoarthritis; Antirheumatic Agents
PubMed: 38942581
DOI: 10.1016/j.rdc.2024.03.003 -
APL Bioengineering Jun 2024Mechanobiology is a rapidly advancing field, with growing evidence that mechanical signaling plays key roles in health and disease. To accelerate mechanobiology-based...
Mechanobiology is a rapidly advancing field, with growing evidence that mechanical signaling plays key roles in health and disease. To accelerate mechanobiology-based drug discovery, novel systems are needed that enable mechanical perturbation of cells in a format amenable to high throughput screening. Here, both a mechanical stretch device and 192-well silicone flexible linear stretch plate were designed and fabricated to meet high throughput technology needs for cell stretch-based applications. To demonstrate the utility of the stretch plate in automation and screening, cell dispensing, liquid handling, high content imaging, and high throughput sequencing platforms were employed. Using this system, an assay was developed as a biological validation and proof-of-concept readout for screening. A mechano-transcriptional stretch response was characterized using focused gene expression profiling measured by RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Gen sequencing. Using articular chondrocytes, a gene expression signature containing stretch responsive genes relevant to cartilage homeostasis and disease was identified. The possibility for integration of other stretch sensitive cell types (e.g., cardiovascular, airway, bladder, gut, and musculoskeletal), in combination with alternative phenotypic readouts (e.g., protein expression, proliferation, or spatial alignment), broadens the scope of high throughput stretch and allows for wider adoption by the research community. This high throughput mechanical stress device fills an unmet need in phenotypic screening technology to support drug discovery in mechanobiology-based disease areas.
PubMed: 38938688
DOI: 10.1063/5.0206852 -
IEEE Transactions on Bio-medical... Jun 2024The high prevalence of osteoarthritis emphasizes the need for a cost-effective and accessible method for its early diagnosis. Recently, the portability and affordability...
OBJECTIVE
The high prevalence of osteoarthritis emphasizes the need for a cost-effective and accessible method for its early diagnosis. Recently, the portability and affordability of very-low-field (VLF) magnetic resonance imaging (MRI, 10-100 mT) have caused it to gain popularity. Nevertheless, there is insufficient evidence to quantify early degenerative changes in cartilage using VLF MRI. This study assessed the potential of T1ρ and T2 mapping for detecting degenerative changes in porcine cartilage specimens using a 50 mT MRI scanner.
METHODS
T2- and T1ρ-weighted images were acquired using a 50 mT MRI scanner with 2D spin-echo and triple-refocused T1ρ preparation sequences. MRI scans of porcine cartilage were also acquired using a 3 T MRI scanner for comparison. A mono-exponential algorithm was applied to fit a series of T2- and T1ρ-weighted images. T2 values for CuSO4·5H2O solutions measured via Carr-Purcell-Meiboom-Gill (CPMG) and spin-echo sequences were compared to verify the algorithm's reliability. The nonparametric Kruskal-Wallis statistical test was used to compare T2 and T1ρ values. Experimental repeatability was assessed using the root-mean-square of the coefficient of variation (rmsCV).
RESULTS
T2 values of the CuSO4·5H2O solutions obtained using the spin-echo sequence showed differences within 2.3% of those obtained using the CPMG sequence, indicating the algorithm's reliability. The T1ρ values for varying concentrations of agarose gel solutions were higher than the T2 values. Furthermore, 50 mT and 3 T MRI results showed that both the T1ρ and T2 values were significantly higher for porcine cartilage degraded for 6 h vs intact cartilage, with p-values of 0.006 and 0.01, respectively. Our experimental results showed good reproducibility (rmsCV < 8%).
CONCLUSION
We demonstrated the feasibility of quantitative cartilage imaging via T2 and T1ρ mapping at 50 mT MRI for the first time.
PubMed: 38935473
DOI: 10.1109/TBME.2024.3420174 -
Nutrients Jun 2024Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life....
Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life. Typically, OA is treated using painkillers and non-steroidal anti-inflammatory drugs (NSAIDs). While current pharmacologic treatments are common, their potential side effects have prompted exploration into functional dietary supplements. Recently, eggshell membrane (ESM) has emerged as a potential functional ingredient for joint and connective tissue disorders due to its clinical efficacy in relieving joint pain and stiffness. Despite promising clinical evidence, the effects of ESM on OA progression and its mechanism of action remain poorly understood. This study evaluated the efficacy of Ovomet, a powdered natural ESM, against joint pain and disease progression in a monosodium iodoacetate (MIA)-induced rodent model of OA in mice and rats. The results demonstrate that ESM significantly alleviates joint pain and attenuates articular cartilage destruction in both mice and rats that received oral supplementation for 5 days prior to OA induction and for 28 days thereafter. Interestingly, ESM significantly inhibited mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as inflammatory mediators, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase in the knee joint cartilage at the early stage of OA, within 7 days after OA induction. However, this effect was not observed in the late stage at 28 days after OA induction. ESM further attenuates the induction of protein expression for cartilage-degrading enzymes like matrix metalloproteinase (MMPs) 3 and 13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in the late-stage. In addition, MIA-induced reduction of the protein expression levels of cartilage components, cartilage oligomeric matrix protein (COMP), aggrecan (ACAN) and collagen type II α-1 chain (COL2α1), and cartilage extracellular matrix (ECM) synthesis promoting transcriptional factor SRY-Box 9 (SOX-9) were increased via ESM treatment in the cartilage tissue. Our findings suggest that Ovomet, a natural ESM powder, is a promising dietary functional ingredient that can alleviate pain, inflammatory response, and cartilage degradation associated with the progression of OA.
Topics: Animals; Egg Shell; Cartilage, Articular; Osteoarthritis; Male; Mice; Nitric Oxide Synthase Type II; Rats; Inflammation; Dietary Supplements; Cytokines; Disease Models, Animal; Rats, Sprague-Dawley; Arthralgia; Time Factors; Iodoacetic Acid; Anti-Inflammatory Agents
PubMed: 38931240
DOI: 10.3390/nu16121885 -
Journal of Personalized Medicine Jun 2024Osteoarthritis (OA) is the most common complex musculoskeletal disorder, resulting from the degeneration of the articular cartilage and characterized by joint pain and...
Osteoarthritis (OA) is the most common complex musculoskeletal disorder, resulting from the degeneration of the articular cartilage and characterized by joint pain and dysfunction that culminate in progressive articular cartilage loss. We present our experience in the management of hip and knee OA by means of the intra-articular injection of fat micrograft, describing our approach, which was developed from the belief in the powerful reparative effect of autologous fat graft on damaged tissue, as well as its natural lubricating effect on the joints. Inclusion criteria were as follows: men and women, aged 20 to 80 years, that referred articular pain of the hips and/or knees, showing initial-stage degenerative OA. From October 2018 to July 2023, a total of 250 patients underwent treatment with the Sefficare device (SEFFILINE srl, Bologna, Italy). The Superficial Enhanced Fluid Fat Injection device was used to perform autologous regenerative treatments in a safe, standardized, easy, and effective way on 160 women, 64%, and 90 men, 36%. A total of 190 procedures (76%) involved the knees, with 20 patients who were bilaterally treated, while 60 procedures, all unilateral, involved the hips (24%). The mean age at treatment was 52.4 years. Before treatment, each patient had undergone X-rays and Magnetic Resonance Imaging (MRI) of the painful hip/knee to evaluate and grade the articular OA. Postoperatively, each patient was assessed after one, three, six, and twelve months. The donor site postoperative course was uneventful other than minimal discomfort. Clinically, the ROM (range of motion) of the treated knee/hip increased an average of 10 degrees 3 months after treatment, but the stiffness was reduced, as reported by the patients. The VAS (Visual Analog Scale) was submitted at 3, 6, and 12 months, demonstrating a progressive reduction of pain, with the best score obtained at six months postoperatively. In total, 85% of patients were satisfied one year after treatment, with a considerable improvement in pain and quality of life. The satisfactory outcome of this minimally invasive procedure indicates that the intra-articular injection of fat micrograft can replace or considerably delay the need for the classical major joint replacement surgery, thanks to its impact on the quality of life of patients and financial cost.
PubMed: 38929825
DOI: 10.3390/jpm14060604