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The Journal of Bone and Joint Surgery.... Apr 2021Management of chondral lesions of the knee is challenging and requires assessment of several factors including the size and location of the lesion, limb alignment and... (Review)
Review
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Management of chondral lesions of the knee is challenging and requires assessment of several factors including the size and location of the lesion, limb alignment and rotation, and the physical and mental health of the individual patient.
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There are a multitude of options to address chondral pathologies of the knee that allow individualized treatment for the specific needs and demands of the patient.
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Osteochondral autograft transfer remains a durable and predictable graft option in smaller lesions (<2 cm2) in the young and active patient population.
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Both mid-term and long-term results for large chondral lesions (≥3 cm2) of the knee have demonstrated favorable results with the use of osteochondral allograft or matrix-associated chondrocyte implantation.
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Treatment options for small lesions (<2 cm2) include osteochondral autograft transfer and marrow stimulation and/or microfracture with biologic adjunct, while larger lesions (≥2 cm2) are typically treated with osteochondral allograft transplantation, particulated juvenile articular cartilage, or matrix-associated chondrocyte implantation.
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Emerging technologies, such as allograft scaffolds and cryopreserved allograft, are being explored for different graft sources to address complex knee chondral pathology; however, further study is needed.
Topics: Bone Transplantation; Cartilage, Articular; Chondrocytes; Humans; Injury Severity Score; Knee Injuries; Knee Joint; Tissue Scaffolds; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome
PubMed: 33470591
DOI: 10.2106/JBJS.20.01161 -
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 -
Drug Metabolism Reviews Nov 2019Articular cartilage has a complex structure and metabolism which allow for a proper movement within joints. Nevertheless, several systemically administered... (Review)
Review
Articular cartilage has a complex structure and metabolism which allow for a proper movement within joints. Nevertheless, several systemically administered pharmacological agents have been proved to improve the anabolic response in the case of cartilage lesions. Alendronate, glucosamine, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, vitamin C, vitamin D, aspirin and strontium ranelate have shown positive results in clinical trials. On the other hand, calcitonin, risedronate, doxycycline, and celecoxib did not slow the progression of cartilage lesions in clinical trials. Other systemic drugs or supplements such as teriparatide, leptin, zoledronic acid, bevacizumab, atorvastatin, omega-3 fatty acid, naringin, MSM, selenium, zinc, magnesium, resveratrol, donepezil, naproxen, etodolac, ursodeoxycholic acid (UDCA), lithium chloride, and rebamipide showed positive results in in vitro and animal studies but clinical trials are needed to confirm the positive impact on cartilage repair. A number of molecules, not currently available on the market, have also shown promising results in cartilage healing, such as licofelone, sclerostin, cyclopamine, cyclodextrin polysulfate, AG-041R, osteoprotegerin, rhMK, β-cryptoxanthine, NF-κb essential modulator binding domain (NBD), TGF-β-neutralizing antibody, osteogenic protein-1 (BMP-7), fibroblast growth factor 2 (FGF2), and RhBMP-2. Currently available systemic drugs that impair cartilage healing are represented by corticosteroids, vitamin A, and fluoroquinolones.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Cartilage, Articular; Cyclooxygenase 2 Inhibitors; Dietary Supplements; Humans; Osteoarthritis; Randomized Controlled Trials as Topic
PubMed: 31726891
DOI: 10.1080/03602532.2019.1687511 -
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 -
Seminars in Musculoskeletal Radiology Jun 2021Osteoarthritis, characterized by the breakdown of articular cartilage and other joint structures, is one of the most prevalent and disabling chronic diseases in the... (Review)
Review
Osteoarthritis, characterized by the breakdown of articular cartilage and other joint structures, is one of the most prevalent and disabling chronic diseases in the United States. Magnetic resonance imaging is a commonly used imaging modality to evaluate patients with joint pain. Both two-dimensional fast spin-echo sequences (2D-FSE) and three-dimensional (3D) sequences are used in clinical practice to evaluate articular cartilage. The 3D sequences have many advantages compared with 2D-FSE sequences, such as their high in-plane spatial resolution, thin continuous slices that reduce the effects of partial volume averaging, and ability to create multiplanar reformat images following a single acquisition. This article reviews the different 3D imaging techniques available for evaluating cartilage morphology, illustrates the strengths and weaknesses of 3D approaches compared with 2D-FSE approaches for cartilage imaging, and summarizes the diagnostic performance of 2D-FSE and 3D sequences for detecting cartilage lesions within the knee and hip joints.
Topics: Cartilage, Articular; Hip Joint; Humans; Imaging, Three-Dimensional; Knee Joint; Magnetic Resonance Imaging
PubMed: 34547805
DOI: 10.1055/s-0041-1730913 -
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 -
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