Search Results (225)

Cartilage regeneration has long been a major challenge in the treatment of osteoarthritis (OA). Aiming to develop a simple outpatient treatment for knee OA, we have demonstrated the potential of combining Nomura’s jellyfish mucin (JM) and hyaluronic acid (HA) to contribute to cartilage repair and regeneration in chondrocytes. In this study, we examined the effects of moon jellyfish JM and jellyfish collagen (JC) on chondrocytes. Polydactyly-derived chondrocytes (PDs), obtained from polydactyly surgery, were used. PDs were cultured in media supplemented with JM or JC, harvested, and evaluated by RT-qPCR. The effects of simultaneous addition of the inflammatory cytokine IL-1β were also examined. Furthermore, the effects on rat articular cartilage were investigated. A mono-iodoacetate (MIA) model was created by intra-articular injection in 6-week-old rats, followed by four intra-articular injections. Evaluations were performed using macroscopic observation and histological assessment with the OARSI scoring system. In vitro, the addition of JM or JC significantly affected the expression of ACAN, MMP3, and ADAMTS5. However, in vivo, intra-articular injection of JM alone did not significantly suppress cartilage degeneration in MIA-induced OA model rats. Both JM and JC may contribute to the suppression of cartilage degeneration as well as to cartilage repair and regeneration, even in the absence of HA. However, further studies are needed to clarify the optimal conditions, such as dosage, timing, and delivery method, that are required to achieve these effects in articular cartilage. Full article

A subset of chondrocytes in various human cartilage tissues, including neoplastic, regenerative, and normal cartilage, expresses α-smooth muscle actin (α-SMA), a protein typically found in smooth muscle cells. These α-SMA-containing chondrocytes, termed myochondrocytes and myochondroblasts, may play important roles in cartilage physiology, regeneration, and structural integrity, particularly in auricular and articular cartilage. This review synthesizes current knowledge regarding the terminology, distribution, and biological significance of these cells across normal, osteoarthritic, transplanted, and neoplastic cartilage. We summarize key findings from immunohistochemical studies using markers such as S-100, α-SMA, and SOX9, along with ultrastructural confirmation of myofilament bundles via electron microscopy. Current evidence suggests that myochondrocytes exhibit enhanced regenerative potential and contribute to matrix remodeling. Furthermore, their presence reflects the inherent cellular heterogeneity of cartilage, potentially arising from transdifferentiation processes involving fibroblasts, mesenchymal stem cells, or chondroblasts. Finally, TGF-β1 and PDGF-BB are identified as a critical modulator of α-SMA expression and chondrocyte phenotype. A deeper understanding of nature and function of myochondrocytes and myochondroblasts may improve interpretations of cartilage pathology and inform strategies for tissue engineering and cartilage repair. This review highlights the need for further investigation into the molecular regulation and functional roles of these cells in both physiological and pathological contexts. Full article

Osteoarthritis (OA) is an inflammatory disorder characterized by metabolic changes in the bone tissue, including the degeneration of hyaline cartilage (articular cartilage) and fibrocartilage (including the meniscus and labrum), sclerosis of the subchondral bone, and osteophyte formation. OA poses a major challenge for adults of all ages, leading to increased morbidity and decreased quality of life. The current conventional therapies mainly focus on pain control, with no definitive or regenerative therapies to reverse OA progression available. Lasers consist of electromagnetic waves generated by radiation emitted by an excited material. In medicine and dentistry, photobiomodulation by low-power laser therapy (photobiomodulation therapy [PBMT]) has been widely applied clinically to promote healing, regenerate tissue, modulate inflammation, and relieve pain. Basic studies have explored the regulation of OA manifestations and joint inflammation using PBMT, as well as the mechanisms of action involved, and clinical research has validated the beneficial effects of PBMT for patients with OA. However, the effects of PBM on OA and its mechanisms of action remain unknown. Herein, we review basic research that has examined the effects of PBMT on OA using in vitro and in vivo testing and discuss future challenges and prospects. Full article

Articular cartilage regeneration remains a major challenge due to its limited self-repair capacity. Bone marrow-derived skeletal stem cells (SSCs) and mesenchymal stem cells (MSCs) are promising candidates for cartilage engineering, although they differ in their chondrogenic potential. This study explored whether co-culturing SSCs and MSCs in three-dimensional (3D) organoid systems under cartilage physioxia (5% O₂) and chondrogenic induction could improve cartilage tissue formation. SSCs, MSCs, and SSC–MSC co-cultures were characterized for morphology, phenotype, and differentiation capacity. Organoids were generated and cultured for 10 days, followed by analysis of morphology, viability, gene expression (SOX9, RUNX2, ACAN, COL2A1, COL10A1, PRG4, and PDPN), chondrocyte-associated antigens (CD44, CD105, CD146, and PDPN), and cartilage ECM proteins (aggrecan, collagen types I, II, and X, and PRG4). SSCs showed robust chondrogenic and osteogenic potential, while MSCs exhibited a balanced multipotency. Co-culture-derived organoids enhanced chondrogenesis and reduced adipogenesis, with higher expression of cartilage-specific ECM and lower hypertrophic marker levels. These findings highlight the functional synergy between SSCs and MSCs in co-culture, promoting the formation of stable, cartilage-like structures under physioxia. The approach offers a promising strategy for generating preclinical models and advancing regenerative therapies for hyaline cartilage repair. Full article

Early-stage knee osteoarthritis (knee OA) lacks effective regenerative therapies. This study aimed to compare the cartilage regenerative effects, clinical efficacy, and safety of intra-articular injections of autologous adipose-derived mesenchymal stem cells (ADSCs) versus hyaluronic acid (HA). Forty-eight patients with early knee OA were enrolled in a prospective open-blinded multi-center study at Suranaree University of Technology Hospital and Phramongkutklao Hospital. Participants were randomized into either the ADSC or HA group. Primary outcomes included MRI-based cartilage lesion volume, synovial thickness via ultrasound, and WOMAC scores over 6 months. MRI results revealed significant and progressive cartilage regeneration in the ADSC group. In particular, medial femoral cartilage lesion volume decreased by 50.06 mm³, whereas the HA group showed an increase of 36.44 mm³. Synovial thickness also declined significantly in the ADSC group at 3 and 6 months. Both groups demonstrated reduced symptoms, but the ADSC group achieved superior and sustained improvements in WOMAC pain, stiffness, and function scores throughout the 6-month follow-up. The clinical benefits were consistent and more pronounced compared with HA. No serious adverse events occurred. In conclusion, intra-articular ADSC injections show superior cartilage restoration on MRI and better clinical outcomes than HA injection, making them a promising treatment for early-stage knee OA. Full article

Articular cartilage (AC) has a very limited capacity for self-healing once damaged. Chondrocytes maintain AC homeostasis and are key cells in AC tissue engineering (ACTE). However, chondrocytes lose their function due to oxidative stress. Umbilical cord mesenchymal stem cells (UCMSCs) are investigated as an alternative cell source for ACTE. MSCs are known to regulate tissue regeneration through host cell modulation, largely via extracellular vesicle (EV)-mediated cell-to-cell communication. The purpose of this study was to verify whether UCMSC-derived EVs (UCMSC-EVs) enhance chondrocyte function. The mean particle sizes of the UCMSC-EVs were 79.8 ± 19.05 nm. Transmission electron microscopy (TEM) revealed that UCMSC-EVs exhibited a spherical morphology. The presence of CD9, CD63, and CD81 confirmed the identity of UCMSC-EVs, with α-tubulin undetected. UCMSC-EVs maintained chondrocyte survival, and increased chondrocyte proliferation after intake by chondrocytes. UCMSC-EVs upregulated mRNA levels of SOX-9, collagen type II (Col-II), and Aggrecan, while decreasing collagen type I (Col-I) levels. UCMSC-EVs reduced the oxidative stress of chondrocytes by reducing mitochondrial superoxide production and increasing protein levels of SOD-2 and Sirt-3 in chondrocytes. The 50 most abundant known microRNAs (miRNAs) derived from UCMSC-EVs were selected for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. GO analysis revealed enrichment in pathways associated with small GTPase-mediated signal transduction, GTPase regulatory activity, and mitochondrial matrix. The KEGG analysis indicated that these miRNAs may regulate chondrocyte function through the PI3K-Akt, MAPK, and cAMP signaling pathways. In summary, this study shows that UCMSC-EVs enhance chondrocyte function and may be applied to ACTE. Full article

Understanding the complex mechanical behavior of osteochondral tissues in silico is essential for improving experimental models and advancing research in joint health and degeneration. This review provides a comprehensive analysis of the constitutive models currently used to represent the different layers of the osteochondral region, from articular cartilage to subchondral bone, including intermediate regions such as the tidemark and the calcified cartilage layer. Each layer exhibits unique structural and mechanical properties, necessitating a layer-specific modeling approach. Through critical comparison of existing mathematical models, the viscoelastic model is suggested as a pragmatic starting point for modeling articular cartilage zones, the tidemark, and the calcified cartilage layer, as it captures essential time-dependent behaviors such as creep and stress relaxation while ensuring computational efficiency for initial coupling studies. On the other hand, a linear elastic model was identified as an optimal starting point for both the subchondral bone plate and the subchondral trabecular bone, reflecting their dense and stiff nature, and providing a coherent framework for early-stage multilayer integration. This layered modeling approach enables the development of physiologically coherent and computationally efficient representations of osteochondral region modeling. Furthermore, by establishing a layer-specific modeling approach, this review paves the way for modular in silico simulations through the coupling of computational models. Such an integrative framework supports scaffold design, in vitro experimentation, preclinical validation, and the mechanobiological exploration of osteochondral degeneration and repair. These efforts are essential for deepening our understanding of tissue responses under both physiological and pathological conditions. Ultimately, this work provides a robust theoretical foundation for future in silico and in vitro studies aimed at advancing osteochondral tissue regeneration strategies. Full article

Articular cartilage is an avascular and aneural connective tissue that is frequently damaged due to trauma or degenerative joint diseases, often resulting in arthritis. Its limited intrinsic capacity for self-renewal poses a significant challenge to effective repair. Hence, the development of regenerative strategies is essential to enhance the poor intrinsic healing of cartilage tissue. Photobiomodulation (PBM) has gained increasing attention as a noninvasive, drug-free, and safe approach. PBM exerts photobiological effects that promote cellular responses and reduce inflammatory conditions, all of which are beneficial for cartilage repair. Nonetheless, the efficacy of PBM varies depending on treatment parameters and treated targets. This review first summarizes PBM parameter-dependent outcomes in cartilage regeneration studies. Reported data indicate frequent use of red lasers (600–660 nm, 0–10 J/cm²), GaAIAs lasers (800–880 nm, 10–50 J/cm²), and Nd:YAG lasers (1064 nm, up to 200 J/cm²) in in vitro, in vivo, and clinical studies. Moreover, PBM in conjunction with cartilage tissue engineering (CTE) has shown synergistic effects, enhancing scaffold-based repair outcomes. This review additionally explores PBM applications within CTE frameworks. The summarized findings aim to inform researchers and physicians by outlining optimized PBM strategies and highlighting PBM’s strong potential in promoting cartilage regeneration, both independently and in combination with CTE. Full article

Developing a functional tissue-engineered articular cartilage remains a challenge to improving clinical treatment of cartilage injury and joint-related degenerative disease. The dynamic self-regenerating cartilage (dSRC) approach presented here encourages autologous chondrocytes to generate their own matrix rather than imposing a matrix upon them. dSRC constructs were grown for 12 weeks under hypoxic conditions in reciprocating motion. Biochemical composition was evaluated, specifically water, collagen, and proteoglycan content. Speckle rHEologicAl micRoscopy (SHEAR) was utilized for spatially resolved evaluation of the shear modulus in engineered cartilage. Histological and immunohistochemical analyses of dSRC were also performed. The maturation of the dSRC matrix results in collagen and glycosaminoglycan (GAG) levels around 50% of those in native cartilage. SHEAR images demonstrate an increase in shear modulus of the matrix to ~20% that of native cartilage after 12 weeks. Histological support for excellent collagen and GAG production was evident, and immunohistochemistry showed a high preference for hyaline-like type II collagen in the neomatrix. A decrease in chondrocyte density occurred from an initial hypercellular matrix to that approaching native cartilage by 12 weeks. While this maturation of dSRC in vitro should not be construed as an absolute prediction of in vivo performance, these results are encouraging, representing a potential new cartilage repair and regeneration approach. Full article

Bone marrow aspirate concentrate (BMAC) is an autologous regenerative therapy enriched with mesenchymal stem cells (MSCs) and bioactive growth factors, offering potential disease-modifying effects in knee osteoarthritis (OA). Compared to conventional intra-articular treatments, including hyaluronic acid (HA), platelet-rich plasma (PRP), and corticosteroids, BMAC promotes cartilage regeneration, modulates inflammation, and enhances subchondral bone remodeling. Clinical evidence suggests that BMAC provides short- to mid-term symptomatic relief and functional improvement, with some studies indicating a potential to delay total knee arthroplasty (TKA). However, findings remain inconsistent, and long-term efficacy compared to PRP or autologous conditioned serum (ACS) is yet to be firmly established. Variability in BMAC preparation methods, injection protocols (single vs. repeated administration, intra-articular vs. subchondral delivery), and patient selection criteria complicates its clinical application, highlighting the need for standardized guidelines. Additionally, economic feasibility and cost-effectiveness concerns limit its widespread adoption. This review synthesizes current clinical evidence, evaluates optimal administration strategies, and explores future directions for improving treatment standardization and patient-specific therapy. Future research should prioritize well-designed, multicenter randomized controlled trials (RCTs) with long-term follow-up to confirm the sustained efficacy and therapeutic potential of BMAC in OA management. Full article

Articular cartilage has limited regenerative potential due to its anatomical characteristics, making complete recovery from damage challenging. Microfracture (MFx) is a widely used technique to promote cartilage healing, often enhanced with scaffolds to improve outcomes. In this study, we compared the efficacy of bilayer atelocollagen and standard collagen scaffolds combined with MFx in treating osteochondral defects in a rabbit model. Three articular cartilage defects were created in the femoral condyle of each rabbit and treated with either MFx plus a bilayer atelocollagen scaffold (test group), MFx plus a standard collagen scaffold (positive group), or MFx alone (negative group). Macroscopic and histological assessments were performed at 3, 6, and 12 weeks. By week 12, macroscopic examination showed hyaline-like cartilage restoration in the test group, while the positive group exhibited restoration with some overgrowth, and the negative group showed no restoration. Histological analysis revealed significantly better restoration in the test group than in the negative group, with comparable outcomes between the test and positive groups. These findings suggest that bilayer atelocollagen scaffold implantation following MFx is a promising treatment for articular cartilage defects and may provide a viable therapeutic option for patients with cartilage damage. Full article

Traumatic or degenerative defects of articular cartilage impair joint function, and the treatment of articular cartilage damage remains a challenge. By mimicking the cartilage extracellular matrix (ECM), exosome-seeded cryogels may enhance cell proliferation and chondral repair. ECM-based cryogels were cryopolymerized with gelatin, chondroitin sulfate, and various concentrations (0%, 0.3%, 0.5%, and 1%) of hyaluronic acid (HA), and their water content, swelling ratio, porosity, mechanical properties, and effects on cell viability were evaluated. The regenerative effects of bone marrow-derived mesenchymal stem cell (BM-MSC)-derived exosome (at a concentration of 10⁶ particles/mL)-seeded 0.3% HA cryogels were assessed in vitro and in surgically induced male New Zealand rabbit cartilage defects in vivo. The water content, swelling ratio, and porosity of the cryogels significantly (p < 0.05) increased and the Young’s modulus values of the cryogels decreased with increasing HA concentrations. MTT assays revealed that the developed biomaterials had no cytotoxic effects. The optimal cryogel composition was 0.3% HA, and the resulting cryogel had favorable properties and suitable mechanical strength. Exosomes alone and exosome-seeded cryogels promoted chondrocyte proliferation (with cell optical densities that were 58% and 51% greater than that of the control). The cryogel alone and the exosome-seeded cryogel facilitated ECM deposition and sulfated glycosaminoglycan synthesis. Although we observed cartilage repair via Alcian blue staining with both the cryogel alone and the exosome-seeded cryogel, the layered arrangement of the chondrocytes was superior to that of the control chondrocytes when exosome-seeded cryogels were used. This study revealed the potential value of using BM-MSC-derived exosome-seeded ECM-based cryogels for cartilage tissue engineering to treat cartilage injury. Full article

Osteochondral defects, involving both articular cartilage and subchondral bone, pose significant challenges to joint function and health due to the lack of spontaneous healing and the risk of long-term degenerative diseases like osteoarthritis. Biomaterials have emerged as important components in the development of scaffolds, providing structural support that facilitates tissue growth, integration, and regeneration. This study aims to demonstrate the effectiveness of a tomographic assessment method for optimizing the evaluation of osteochondral regeneration, particularly using Hounsfield units, to enable the evaluation of scaffold integration and tissue regeneration. The sheep model was selected as a model study. Two distinct configurations of biomaterials were utilized in this study: Honey (HMG—Mg doped hydroxyapatite; HWS—wollastonite–hydroxyapatite) and Bi-layer (BWS—wollastonite–hydroxyapatite). The HMG scaffold demonstrated superior integration, reparative tissue quality, and regeneration potential compared to the HWS, BWS, and CTRL groups. The findings underscore the significance of CT assessment as a preliminary method for evaluating hard tissue, such as bone, employing Hounsfield units. Statistical evaluations validated the significant differences in performance, particularly favoring the HMG group. The results of this study underscore the importance of tomographic assessment in evaluation of osteochondral regeneration. Full article

Antlers, as the only fully regenerable bone tissue in mammals, serve as an exceptional model for investigating bone growth, mineralization, articular cartilage repair, and the pathophysiology of osteoporosis. Nevertheless, the exact molecular mechanisms governing osteogenesis, particularly the dynamic cellular interactions and signaling pathways coordinating these processes, remain poorly characterized. This study used single-cell RNA sequencing (scRNA-seq) on the 10× Genomics Chromium platform, combined with bulk-RNA sequencing results, to comprehensively analyze molecular regulatory mechanisms in rapid antler osteogenesis. The results showed that eight cell types were identified in sika deer antler during the growth and ossification stages: mesenchymal, chondrocyte, osteoblast, pericyte, endothelial, monocyte/macrophage, osteoclast, and NK cells. Chondrocytes were predominantly found during the growth stage, while osteoblasts were more abundant during the ossification stage. Mesenchymal cells were subclassified into three subcategories: MSC_1 (VCAN and SFRP2), MSC_2 (TOP2A, MKI67), and MSC_3 (LYVE1 and TNN). MSC_3 was predominantly present during the growth stage. During the growth stage, MSC_1 and MSC_2 upregulated genes related to vasculature development (COL8A1, NRP1) and cell differentiation (PTN, SFRP2). During the ossification stage, these subcategories upregulated genes involved in the positive regulation of p53 class mediator signal transduction (RPL37, RPL23, RPS20, and RPL26), osteoblast differentiation (SPP1, IBSP, BGLAP), and proton-motive ATP synthesis (NDUFA7, NDUFB3, NDUFA3, NDUFB1). Endothelial cells were categorized into five subpopulations: Enc_1 (SPARCL1, VWF), Enc_2 (MCM5), Enc_3 (ASPM, MKI67), Enc_4 (SAT1, CXCL12), and Enc_5 (ZFHX4, COL6A3). Combined scRNA-seq and bulk RNA-seq analysis revealed that the ossification stage’s upregulation genes included osteoclast- and endothelial cell-specific genes, while the growth stage’s upregulation genes were mainly linked to collagen organization, osteoblast differentiation, mitotic cell cycle, and chondrocyte differentiation. Overall, this study offers a detailed single-cell analysis of gene expression patterns in antlers during the growth and ossification stages, providing insights into the molecular mechanisms driving rapid osteogenesis. Full article

Background: Articular chondrocytes are specialized cells in synovial joint cartilage, responsible for maintaining and regenerating the extracellular matrix. Inflammation disrupts the balance between matrix synthesis and degradation, leading to cartilage breakdown. This process, commonly observed in conditions such as osteoarthritis, results in chondrocyte dysfunction and accelerates joint degeneration. Since TRPA1 channels are implicated in inflammatory processes, this study investigates the expression of TRPA1 channels in freshly dissociated rat articular chondrocytes and their modulation by anti-inflammatory agents. Methods: We used the whole-cell patch-clamp method to assess TRPA1 channel expression and modulation. Results: Freshly dissociated chondrocytes exhibit ion currents attributable to TRPA1 channel expression, with higher magnitudes observed in medium-sized cells. These currents decrease over time in primary culture. Treatment with pro-inflammatory agents (IL-1α, IL-1β, and LPS) increases TRPA1′s current magnitude. IL-1β treatment directly induces transient TRPA1 currents. Several signaling components activated during inflammation contribute to the IL-1β-induced enhancement of TRPA1 current density, including IL-1 R1, the adaptor protein MyD88, and the downstream kinases IRAK1 and IRAK4. Conclusions: Our findings demonstrate that healthy rat chondrocytes express functional TRPA1 channels and that inflammatory processes modulate their expression. Full article