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Matrix Biology : Journal of the... Oct 2018Hyaline cartilages, fibrocartilages and elastic cartilages play multiple roles in the human body including bearing loads in articular joints and intervertebral discs,... (Review)
Review
Hyaline cartilages, fibrocartilages and elastic cartilages play multiple roles in the human body including bearing loads in articular joints and intervertebral discs, providing joint lubrication, forming the external ears and nose, supporting the trachea, and forming the long bones during development and growth. The structure and organization of cartilage's extracellular matrix (ECM) are the primary determinants of normal function. Most diseases involving cartilage lead to dramatic changes in the ECM which can govern disease progression (e.g., in osteoarthritis), cause the main symptoms of the disease (e.g., dwarfism caused by genetically inherited mutations) or occur as collateral damage in pathological processes occurring in other nearby tissues (e.g., osteochondritis dissecans and inflammatory arthropathies). Challenges associated with cartilage diseases include poor understanding of the etiology and pathogenesis, delayed diagnoses due to the aneural nature of the tissue and drug delivery challenges due to the avascular nature of adult cartilages. This narrative review provides an overview of the clinical and pathological features as well as current treatment options available for various cartilage diseases. Late breaking advances are also described in the quest for development and delivery of effective disease modifying drugs for cartilage diseases including osteoarthritis, the most common form of arthritis that affects hundreds of millions of people worldwide.
Topics: Cartilage Diseases; Cartilage, Articular; Disease Progression; Extracellular Matrix; Humans; Mutation
PubMed: 29803938
DOI: 10.1016/j.matbio.2018.05.005 -
Arthritis Research & Therapy Jul 2022Osteoarthritis (OA) is an age-related cartilage degenerative disease, and chondrocyte senescence has been extensively studied in recent years. Increased numbers of... (Review)
Review
Osteoarthritis (OA) is an age-related cartilage degenerative disease, and chondrocyte senescence has been extensively studied in recent years. Increased numbers of senescent chondrocytes are found in OA cartilage. Selective clearance of senescent chondrocytes in a post-traumatic osteoarthritis (PTOA) mouse model ameliorated OA development, while intraarticular injection of senescent cells induced mouse OA. However, the means and extent to which senescence affects OA remain unclear. Here, we review the latent mechanism of senescence in OA and propose potential therapeutic methods to target OA-related senescence, with an emphasis on immunotherapies. Natural killer (NK) cells participate in the elimination of senescent cells in multiple organs. A relatively comprehensive discussion is presented in that section. Risk factors for OA are ageing, obesity, metabolic disorders and mechanical overload. Determining the relationship between known risk factors and senescence will help elucidate OA pathogenesis and identify optimal treatments.
Topics: Animals; Cartilage Diseases; Cartilage, Articular; Cellular Senescence; Chondrocytes; Mice; Osteoarthritis
PubMed: 35869508
DOI: 10.1186/s13075-022-02859-x -
Cartilage Dec 2021Cartilage defects in the knee are being diagnosed with increased frequency and are treated with a variety of techniques. The aim of any cartilage repair procedure is to... (Review)
Review
Cartilage defects in the knee are being diagnosed with increased frequency and are treated with a variety of techniques. The aim of any cartilage repair procedure is to generate the highest tissue quality, which might correlate with improved clinical outcomes, return-to-sport, and long-term durability. Minced cartilage implantation (MCI) is a relatively simple and cost-effective technique to transplant autologous cartilage fragments in a single-step procedure. Minced cartilage has a strong biologic potential since autologous, activated non-dedifferentiated chondrocytes are utilized. It can be used both for small and large cartilage lesions, as well as for osteochondral lesions. As it is purely an autologous and homologous approach, it lacks a significant regulatory oversight process and can be clinically adopted without such limitations. The aim of this narrative review is to provide an overview of the current evidence supporting autologous minced cartilage implantation.
Topics: Cartilage Diseases; Cartilage, Articular; Chondrocytes; Humans; Knee Joint; Transplantation, Autologous
PubMed: 32715735
DOI: 10.1177/1947603520942952 -
Journal of Bone and Mineral Research :... Feb 2019Phenotypic variation in skeletal traits and diseases is the product of genetic and environmental factors. Epigenetic mechanisms include information-containing factors,... (Review)
Review
Phenotypic variation in skeletal traits and diseases is the product of genetic and environmental factors. Epigenetic mechanisms include information-containing factors, other than DNA sequence, that cause stable changes in gene expression and are maintained during cell divisions. They represent a link between environmental influences, genome features, and the resulting phenotype. The main epigenetic factors are DNA methylation, posttranslational changes of histones, and higher-order chromatin structure. Sometimes non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are also included in the broad term of epigenetic factors. There is rapidly expanding experimental evidence for a role of epigenetic factors in the differentiation of bone cells and the pathogenesis of skeletal disorders, such as osteoporosis and osteoarthritis. However, different from genetic factors, epigenetic signatures are cell- and tissue-specific and can change with time. Thus, elucidating their role has particular difficulties, especially in human studies. Nevertheless, epigenomewide association studies are beginning to disclose some disease-specific patterns that help to understand skeletal cell biology and may lead to development of new epigenetic-based biomarkers, as well as new drug targets useful for treating diffuse and localized disorders. Here we provide an overview and update of recent advances on the role of epigenomics in bone and cartilage diseases. © 2019 American Society for Bone and Mineral Research.
Topics: Animals; Cartilage Diseases; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; MicroRNAs; RNA, Long Noncoding
PubMed: 30715766
DOI: 10.1002/jbmr.3662 -
Annals of the New York Academy of... Nov 2016The homeostasis of skeletal tissues requires tight regulation of a variety of signaling pathways, and the onset and progression of skeletal diseases are often caused by... (Review)
Review
The homeostasis of skeletal tissues requires tight regulation of a variety of signaling pathways, and the onset and progression of skeletal diseases are often caused by signaling abnormalities. MicroRNAs (miRNAs) are short noncoding RNA molecules that have emerged as a new dimension of gene regulation. MiRNAs have been shown to play an important role in the regulation of the differentiation of embryonic and hematopoietic stem cells. However, the role of specific miRNAs and their target genes has not been fully defined in the regulation of mesenchymal stem cells. Runx2 is a key transcription factor controlling MSC differentiation and bone and cartilage function. This article reviews work on Runx2 and miRNA regulation in bone and cartilage diseases.
Topics: Animals; Bone Diseases; Cartilage Diseases; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Humans; MicroRNAs
PubMed: 27526290
DOI: 10.1111/nyas.13206 -
Cartilage Dec 2021Mitochondria are recognized to be one of the most important organelles in chondrocytes for their role in triphosphate (ATP) generation through aerobic phosphorylation.... (Review)
Review
PURPOSE OF REVIEW
Mitochondria are recognized to be one of the most important organelles in chondrocytes for their role in triphosphate (ATP) generation through aerobic phosphorylation. Mitochondria also participate in many intracellular processes involving modulating reactive oxygen species (ROS), responding to instantaneous hypoxia stress, regulating cytoplasmic transport of calcium ion, and directing mitophagy to maintain the homeostasis of individual chondrocytes.
DESIGNS
To summarize the specific role of mitochondria in chondrocytes, we screened related papers in PubMed database and the search strategy is ((mitochondria) AND (chondrocyte)) AND (English [Language]). The articles published in the past 5 years were included and 130 papers were studied.
RESULTS
In recent years, the integrity of mitochondrial structure has been regarded as a prerequisite for normal chondrocyte survival and defect in mitochondrial function has been found in cartilage-related diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, the understanding of mitochondria in cartilage is still largely limited. The mechanism on how the changes in mitochondrial structure and function directly lead to the occurrence and development of cartilage-related diseases remains to be elusive.
CONCLUSION
This review aims to summarize the role of mitochondria in chondrocytes under the physiological and pathological changes from ATP generation, calcium homeostasis, redox regulation, mitophagy modulation, mitochondria biogenesis to immune response activation. The enhanced understanding of molecular mechanisms in mitochondria might offer some new cues for cartilage remodeling and pathological intervention.
Topics: Arthritis, Rheumatoid; Cartilage Diseases; Chondrocytes; Humans; Mitochondria; Osteoarthritis
PubMed: 34894777
DOI: 10.1177/19476035211063858 -
Annals of the Rheumatic Diseases Apr 1990Zonal necrosis of chondrocytes is a characteristic feature of Kashin-Beck disease. Inferences about chondronecrosis in several spontaneous and experimental arthropathies... (Comparative Study)
Comparative Study Review
Zonal necrosis of chondrocytes is a characteristic feature of Kashin-Beck disease. Inferences about chondronecrosis in several spontaneous and experimental arthropathies of other species may be relevant to the cause of Kashin-Beck disease and conceivably, too, banal osteoarthritis in man.
Topics: Animals; Cartilage Diseases; Dogs; Humans; Necrosis; Osteochondritis
PubMed: 2187418
DOI: 10.1136/ard.49.4.262 -
Journal of Dental Research Nov 2016Primary cilia, present on most mammalian cells, function as a sensor to sense the environment change and transduce signaling. Loss of primary cilia causes a group of... (Review)
Review
Primary cilia, present on most mammalian cells, function as a sensor to sense the environment change and transduce signaling. Loss of primary cilia causes a group of human pleiotropic syndromes called Ciliopathies. Some of the ciliopathies display skeletal dysplasias, implying the important role of primary cilia in skeletal development and homeostasis. Emerging evidence has shown that loss or malfunction of primary cilia or ciliary proteins in bone and cartilage is associated with developmental and function defects. Intraflagellar transport (IFT) proteins are essential for cilia formation and/or function. In this review, we discuss the role of primary cilia and IFT proteins in the development of bone and cartilage, as well as the differentiation and mechanotransduction of mesenchymal stem cells, osteoblasts, osteocytes, and chondrocytes. We also include the role of primary cilia in tooth development and highlight the current advance of primary cilia and IFT proteins in the pathogenesis of cartilage diseases, including osteoarthritis, osteosarcoma, and chondrosarcoma.
Topics: Animals; Bone Diseases; Carrier Proteins; Cartilage; Cartilage Diseases; Cell Differentiation; Cilia; Flagella; Humans; Mechanotransduction, Cellular; Odontogenesis; Osteogenesis; Protein Transport
PubMed: 27250654
DOI: 10.1177/0022034516652383 -
International Journal of Molecular... Dec 2023Cartilage plays a crucial role in the human body by forming long bones during development and growth to bear loads on joints and intervertebral discs. However, the... (Review)
Review
Cartilage plays a crucial role in the human body by forming long bones during development and growth to bear loads on joints and intervertebral discs. However, the increasing prevalence of cartilage degenerative disorders is a growing public health concern, especially due to the poor innate regenerative capacity of cartilage. Chondrocytes are a source of several inflammatory mediators that play vital roles in the pathogenesis of cartilage disorders. Among these mediators, chemokines have been explored as potential contributors to cartilage degeneration and regeneration. Our review focuses on the progress made during the last ten years in identifying the regulators and roles of chemokines and their receptors in different mechanisms related to chondrocytes and cartilage. Recent findings have demonstrated that chemokines influence cartilage both positively and negatively. Their induction and involvement in either process depends on the local molecular environment and is both site- and time-dependent. One of the challenges in defining the role of chemokines in cartilage pathology or regeneration is the apparent redundancy in the interaction of chemokines with their receptors. Hence, it is crucial to determine, for each situation, whether targeting specific chemokines or their receptors will help in developing effective therapeutic strategies for cartilage repair.
Topics: Humans; Cartilage; Chondrocytes; Chemokines; Cartilage Diseases; Inflammation Mediators
PubMed: 38203552
DOI: 10.3390/ijms25010381 -
Osteoarthritis and Cartilage Mar 2021Stromal cell-derived factor 1 (SDF-1), also known as CXC motif chemokine ligand 12 (CXCL12), is recognized as a homeostatic cytokine with strong chemotactic potency. It... (Review)
Review
Stromal cell-derived factor 1 (SDF-1), also known as CXC motif chemokine ligand 12 (CXCL12), is recognized as a homeostatic cytokine with strong chemotactic potency. It plays an important role in physiological and pathological processes, such as the development of multiple tissues and organs, the regulation of cell distribution, and tumour metastasis. SDF-1 has two receptors, CXC chemokine receptor type 4 (CXCR4) and CXC chemokine receptor type 7 (CXCR7). SDF-1 affects the proliferation, survival, differentiation and maturation of chondrocytes by binding to CXCR4 on chondrocytes. Therefore, SDF-1 has been used as an exogenous regulatory target in many studies to explore the mechanism of cartilage development. SDF-1 is also a potential therapeutic target for osteoarthritis (OA) and rheumatoid arthritis (RA), because of its role in pathological initiation and regulation. In addition, SDF-1 shows potent capacity in the repair of cartilage defects by recruiting endogenous stem cells in a cartilage tissue engineering context. To summarize the specific role of SDF-1 on cartilage development and disease, all articles had been screened out in PubMed by May 30, 2020. The search was limited to studies published in English. Search terms included SDF-1; CXCL12; CXCR4; chondrocyte; cartilage; OA; RA, and forty-seven papers were studied. Besides, we reviewed references in the articles we searched to get additional relevant backgrounds. The review aims to conclude the current knowledge regarding the physiological and pathological role of SDF-1 on the cartilage and chondrocyte. More investigations are required to determine methods targeted SDF-1 to cartilage development and interventions to cartilage diseases.
Topics: Arthritis, Rheumatoid; Cartilage Diseases; Cell Differentiation; Cell Proliferation; Cell Survival; Chemokine CXCL12; Chondrocytes; Chondrogenesis; Humans; Osteoarthritis; Receptors, CXCR; Receptors, CXCR4
PubMed: 33253889
DOI: 10.1016/j.joca.2020.10.010