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Nature Reviews. Rheumatology Jan 2015Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint... (Review)
Review
Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.
Topics: Biocompatible Materials; Biological Factors; Cartilage, Articular; Chondrocytes; Humans; Knee Injuries; Knee Joint; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Prospective Studies; Randomized Controlled Trials as Topic; Regeneration; Tissue Engineering; Tissue Scaffolds; Wound Healing
PubMed: 25247412
DOI: 10.1038/nrrheum.2014.157 -
Cell and Tissue Research Oct 2017The degradation of cartilage in the human body is impacted by aging, disease, genetic predisposition and continued insults resulting from daily activity. The burden of... (Review)
Review
The degradation of cartilage in the human body is impacted by aging, disease, genetic predisposition and continued insults resulting from daily activity. The burden of cartilage defects (osteoarthritis, rheumatoid arthritis, intervertebral disc damage, knee replacement surgeries, etc.) is daunting in light of substantial economic and social stresses. This review strives to broaden the scope of regenerative medicine and tissue engineering approaches used for cartilage repair by comparing and contrasting the anatomical and functional nature of the meniscus, articular cartilage (AC) and nucleus pulposus (NP). Many review papers have provided detailed evaluations of these cartilages and cartilage-like tissues individually but none have comprehensively examined the parallels and inconsistencies in signaling, genetic expression and extracellular matrix composition between tissues. For the first time, this review outlines the importance of understanding these three tissues as unique entities, providing a comparative analysis of anatomy, ultrastructure, biochemistry and function for each tissue. This novel approach highlights the similarities and differences between tissues, progressing research toward an understanding of what defines each tissue as distinctive. The goal of this paper is to provide researchers with the fundamental knowledge to correctly engineer the meniscus, AC and NP without inadvertently developing the wrong tissue function or biochemistry.
Topics: Animals; Biomechanical Phenomena; Cartilage, Articular; Collagen; Humans; Meniscus; Nucleus Pulposus; Regeneration; Tissue Engineering
PubMed: 28413859
DOI: 10.1007/s00441-017-2613-0 -
Osteoarthritis and Cartilage Mar 2022Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality... (Review)
Review
Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality of life in the elderly population. Although the prevalence of OA increases with age, its specific mechanisms have not been elucidated and effective therapeutic disease-modifying drugs have not been developed. As essential organelles in chondrocytes, mitochondria supply energy and play vital roles in cellular metabolism, proliferation and apoptosis. Mitochondrial quality control (MQC) is the key mechanism to coordinate various mitochondrial biofunctions, primarily through mitochondrial biogenesis, dynamics, autophagy and the newly discovered mitocytosis. An increasing number of studies have revealed that a loss of MQC homeostasis contributes to the cartilage damage during the occurrence and development of OA. Several master MQC-associated signaling pathways and regulators exert chondroprotective roles in OA, while cartilage damage-related molecular mechanisms have been partially identified. In this review, we summarized known mechanisms mediated by dysregulated MQC in the pathogenesis of OA and latent bioactive ingredients and drugs for the prevention and treatment of OA through the maintenance of MQC.
Topics: Autophagy; Cartilage, Articular; Chondrocytes; Down-Regulation; Humans; Mitochondria; Osteoarthritis; Oxidative Stress; Reactive Oxygen Species; Up-Regulation
PubMed: 34715366
DOI: 10.1016/j.joca.2021.10.009 -
Experimental & Molecular Medicine Nov 2021Osteoarthritis (OA) is the most common form of arthritis. It is characterized by progressive destruction of articular cartilage and the development of chronic pain and... (Review)
Review
Osteoarthritis (OA) is the most common form of arthritis. It is characterized by progressive destruction of articular cartilage and the development of chronic pain and constitutes a considerable socioeconomic burden. Currently, pharmacological treatments mostly aim to relieve the OA symptoms associated with inflammation and pain. However, with increasing understanding of OA pathology, several potential therapeutic targets have been identified, enabling the development of disease-modifying OA drugs (DMOADs). By targeting inflammatory cytokines, matrix-degrading enzymes, the Wnt pathway, and OA-associated pain, DMOADs successfully modulate the degenerative changes in osteoarthritic cartilage. Moreover, regenerative approaches aim to counterbalance the loss of cartilage matrix by stimulating chondrogenesis in endogenous stem cells and matrix anabolism in chondrocytes. Emerging strategies include the development of senolytic drugs or RNA therapeutics to eliminate the cellular or molecular sources of factors driving OA. This review describes the current developmental status of DMOADs and the corresponding results from preclinical and clinical trials and discusses the potential of emerging therapeutic approaches to treat OA.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Cartilage, Articular; Combined Modality Therapy; Cytokines; Disease Management; Disease Susceptibility; Drug Development; Humans; Molecular Targeted Therapy; Osteoarthritis; Signal Transduction
PubMed: 34848838
DOI: 10.1038/s12276-021-00710-y -
ELife Apr 2023The progenitor cells that form articular cartilage express a gene for a protein called NFATc1, which stops articular chondrocytes from developing too early in the joint.
The progenitor cells that form articular cartilage express a gene for a protein called NFATc1, which stops articular chondrocytes from developing too early in the joint.
Topics: Cell Differentiation; Chondrocytes; Cartilage, Articular; Stem Cells
PubMed: 37017508
DOI: 10.7554/eLife.87355 -
Nature Communications Feb 2023Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal...
Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as are remodeled as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage; however further assessment of functional recovery long term after load bearing injuries is required.
Topics: Animals; Cartilage, Articular; Induced Pluripotent Stem Cells; Primates; Organoids; Hematopoietic Stem Cell Transplantation; Chondrocytes
PubMed: 36808132
DOI: 10.1038/s41467-023-36408-0 -
Cartilage Dec 2021Since the first introduction of the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score, significant progress has been made with regard to surgical...
OBJECTIVE
Since the first introduction of the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score, significant progress has been made with regard to surgical treatment options for cartilage defects, as well as magnetic resonance imaging (MRI) of such defects. Thus, the aim of this study was to introduce the MOCART 2.0 knee score - an incremental update on the original MOCART score - that incorporates this progression.
MATERIALS AND METHODS
The volume of cartilage defect filling is now assessed in 25% increments, with hypertrophic filling of up to 150% receiving the same scoring as complete repair. Integration now assesses only the integration to neighboring native cartilage, and the severity of surface irregularities is assessed in reference to cartilage repair length rather than depth. The signal intensity of the repair tissue differentiates normal signal, minor abnormal, or severely abnormal signal alterations. The assessment of the variables "subchondral lamina," "adhesions," and "synovitis" was removed and the points were reallocated to the new variable "bony defect or bony overgrowth." The variable "subchondral bone" was renamed to "subchondral changes" and assesses minor and severe edema-like marrow signal, as well as subchondral cysts or osteonecrosis-like signal. Overall, a MOCART 2.0 knee score ranging from 0 to 100 points may be reached. Four independent readers (two expert readers and two radiology residents with limited experience) assessed the 3 T MRI examinations of 24 patients, who had undergone cartilage repair of a femoral cartilage defect using the new MOCART 2.0 knee score. One of the expert readers and both inexperienced readers performed two readings, separated by a four-week interval. For the inexperienced readers, the first reading was based on the evaluation sheet only. For the second reading, a newly introduced atlas was used as an additional reference. Intrarater and interrater reliability was assessed using intraclass correlation coefficients (ICCs) and weighted kappa statistics. ICCs were interpreted according to Koo and Li; weighted kappa statistics were interpreted according to the criteria of Landis and Koch.
RESULTS
The overall intrarater (ICC = 0.88, < 0.001) as well as the interrater (ICC = 0.84, < 0.001) reliability of the expert readers was almost perfect. Based on the evaluation sheet of the MOCART 2.0 knee score, the overall interrater reliability of the inexperienced readers was poor (ICC = 0.34, < 0.019) and improved to moderate (ICC = 0.59, = 0.001) with the use of the atlas.
CONCLUSIONS
The MOCART 2.0 knee score was updated to account for changes in the past decade and demonstrates almost perfect interrater and intrarater reliability in expert readers. In inexperienced readers, use of the atlas may improve interrater reliability and, thus, increase the comparability of results across studies.
Topics: Cartilage, Articular; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Reproducibility of Results; Transplantation, Autologous
PubMed: 31422674
DOI: 10.1177/1947603519865308 -
Organogenesis Dec 2023Articular cartilage is a common cartilage type found in a multitude of joints throughout the human body. However, cartilage is limited in its regenerative capacity. A... (Review)
Review
Articular cartilage is a common cartilage type found in a multitude of joints throughout the human body. However, cartilage is limited in its regenerative capacity. A range of methods have been employed to aid adults under the age of 45 with cartilage defects, but other cartilage pathologies such as osteoarthritis are limited to non-steroidal anti-inflammatory drugs and total joint arthroplasty. Cell therapies and synthetic biology can be utilized to assist not only cartilage defects but have the potential as a therapeutic approach for osteoarthritis as well. In this review, we will cover current cell therapy approaches for cartilage defect regeneration with a focus on autologous chondrocyte implantation and matrix autologous chondrocyte implantation. We will then discuss the potential of stem cells for cartilage repair in osteoarthritis and the use of synthetic biology to genetically engineer cells to promote cartilage regeneration and potentially reverse osteoarthritis.
Topics: Adult; Humans; Cartilage, Articular; Cartilage Diseases; Stem Cells; Cell- and Tissue-Based Therapy; Osteoarthritis
PubMed: 37963189
DOI: 10.1080/15476278.2023.2278235 -
Cell Communication and Signaling : CCS May 2022Osteoarthritis (OA) is one of the main causes of disabilities among older people. To date, multiple disease-related molecular networks in OA have been identified,... (Review)
Review
Osteoarthritis (OA) is one of the main causes of disabilities among older people. To date, multiple disease-related molecular networks in OA have been identified, including abnormal mechanical loadings and local inflammation. These pathways have not, however, properly elucidated the mechanism of OA progression. Recently, sufficient evidence has suggested that rhythmic disturbances in the central nervous system (CNS) and local joint tissues affect the homeostasis of joint and can escalate pathological changes of OA. This is accompanied with an exacerbation of joint symptoms that interfere with the rhythm of CNS in reverse. Eventually, these processes aggravate OA progression. At present, the crosstalk between joint tissues and biological rhythm remains poorly understood. As such, the mechanisms of rhythm changes in joint tissues are worth study; in particular, research on the effect of rhythmic genes on metabolism and inflammation would facilitate the understanding of the natural rhythms of joint tissues and the OA pathology resulting from rhythm disturbance. Video Abstract.
Topics: Aged; Cartilage, Articular; Humans; Inflammation; Osteoarthritis
PubMed: 35610652
DOI: 10.1186/s12964-022-00891-7 -
Frontiers in Bioscience (Landmark... Mar 2024Osteoarthritis (OA) is now considered as a multifaceted disease affecting various articular tissues, including cartilage, bone, synovium, and surrounding ligaments. The... (Review)
Review
Osteoarthritis (OA) is now considered as a multifaceted disease affecting various articular tissues, including cartilage, bone, synovium, and surrounding ligaments. The pathophysiology strongly implicates intricate chemical communication, primarily through cytokines, leading to the production of degradative enzymes in cartilage, inflammatory peptides in synovium, and structural changes in bone, resulting in characteristic clinical features such as joint deformities and loss of cartilage space seen on X-rays. Recent studies highlight the previously underestimated role of subchondral bone in OA, revealing its permeability to cytokines and raising questions about the influence of abnormal perfusion on OA pathophysiology, suggesting a vascular component in the disease's etiology. In essence, alterations in bone perfusion, including reduced venous outflow and intraosseous hypertension, play a crucial role in influencing the physicochemical environment of subchondral bone, impacting osteoblast cytokine expression and contributing to trabecular remodeling, changes in chondrocyte phenotype, and ultimately cartilage matrix degeneration in OA. Dynamic contrast (gadolinium) enhanced magnetic resonance imaging (DCE-MRI) was used to quantify perfusion kinetics in normal and osteoarthritic subchondral bone, demonstrating that decreased perfusion temporally precedes and spatially correlates with cartilage lesions in both young Dunkin-Hartley (D-H) guinea pigs and humans with osteoarthritis. Pharmacokinetic analysis of DCE-MRI generated data reveals decreased tracer clearance and outflow obstruction in the medial tibial plateau of osteoarthritic guinea pigs, coinciding with progressive cartilage degradation, loss of Safranin O staining, and increased expression of matrix metalloproteinases and interleukin-1. Positron emission tomographic (PET) scanning using 18F-Fluoride reveals a relationship among bone blood flow, cartilage lesions, and 18F-Fluoride influx rate in OA, highlighting the intricate relationships between decreased perfusion, altered bone metabolism, and the progression of osteoarthritis. These findings, supported by 18F-Fluoride PET data, suggest the presence of venous stasis associated with outflow obstruction, emphasizing the role of decreased subchondral bone perfusion in the pathophysiology of OA and its association with reduced osteoblast activity and advanced cartilage degeneration.
Topics: Humans; Animals; Guinea Pigs; Cartilage, Articular; Fluorides; Osteoarthritis; Vascular Diseases; Cytokines
PubMed: 38538286
DOI: 10.31083/j.fbl2903113