-
Tissue & Cell Feb 2023In the synovial joints the transition between the soft articular cartilage and the subchondral bone is mediated by a layer of calcified cartilage of structural and...
In the synovial joints the transition between the soft articular cartilage and the subchondral bone is mediated by a layer of calcified cartilage of structural and mechanical characteristics closer to those of bone. This layer, buried in the depth of articular cartilage, is not directly accessible and is mostly visualized in histological sections of decalcified tissue, where it appears as a darker strip in contact with the subchondral bone. In this study conventional histology and scanning electron microscopy (SEM) with secondary electron imaging (SE) or backscattered electron imaging (BSE) were used to discriminate the calcified and the uncalcified cartilage in high resolution on native, untreated tissue as well as in deproteinated or demineralized tissue. This approach evidenced a high heterogeneity of the calcified layer of articular cartilage. High resolution pictures revealed that the mineralization process originates by progressive accretion and confluence of individual, small mineral clusters, in a very different way from other hard tissues such as bone, dentin and mineralized tendons. Finally, selective removal of the soft matrix by thermal treatment allowed for the first time a face-on, unrestricted 3D view of the mineralization front.
Topics: Cartilage, Articular; Bone and Bones
PubMed: 36516570
DOI: 10.1016/j.tice.2022.101993 -
Radiologie (Heidelberg, Germany) Apr 2023Acute and chronic cartilage injuries are often encountered in professional and recreational athletes. They can compromise the athlete's performance and career and are... (Review)
Review
BACKGROUND
Acute and chronic cartilage injuries are often encountered in professional and recreational athletes. They can compromise the athlete's performance and career and are considered a potential risk factor for early joint degeneration.
OBJECTIVES
Incidence of cartilage injury in athletes, understanding of cartilage composition, injury mechanism and suitable diagnostic imaging are summarized and established therapeutic procedures, postoperative imaging including detection of relevant complications and assessment of reasonable indications for follow-up examinations are described.
METHODS
Original research and review articles were analyzed.
RESULTS
Cartilage injury can mimic meniscal or ligamentous injury and cannot be ruled out by clinical examination alone. Magnetic resonance imaging (MRI) is the method of choice to (1) detect (sensitivity 87-93%, specificity 94-99%) and grade cartilage lesions to facilitate choice of therapy and (2) to exclude concomitant injuries that require treatment to improve the prognosis of the chosen cartilage therapy. Postoperatively MRI allows noninvasive assessment of the repaired cartilage tissue and is an appropriate method to detect therapeutically relevant complications.
CONCLUSIONS
Knowledge of mechanisms and appearance of cartilage injuries, current cartilage repair techniques and their imaging is crucial for the medical care of athletes.
Topics: Humans; Cartilage, Articular; Knee Joint; Knee Injuries; Cartilage Diseases; Athletes
PubMed: 36877296
DOI: 10.1007/s00117-023-01128-5 -
ELife Feb 2023The origin and differentiation mechanism of articular chondrocytes remain poorly understood. Broadly, the difference in developmental mechanisms of articular and...
The origin and differentiation mechanism of articular chondrocytes remain poorly understood. Broadly, the difference in developmental mechanisms of articular and growth-plate cartilage is still less elucidated. Here, we identified that the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) is a crucial regulator of articular, but not growth-plate, chondrocyte differentiation during development. At the early stage of mouse knee development (embryonic day 13.5), NFATc1-expressing cells were mainly located in the flanking region of the joint interzone. With development, NFATc1-expressing cells generated almost all articular chondrocytes but not chondrocytes in limb growth-plate primordium. NFATc1-expressing cells displayed prominent capacities for colony formation and multipotent differentiation. Transcriptome analyses revealed a set of characteristic genes in NFATc1-enriched articular cartilage progenitors. Strikingly, the expression of NFATc1 was diminished with articular chondrocyte differentiation, and suppressing NFATc1 expression in articular cartilage progenitors was sufficient to induce spontaneous chondrogenesis while overexpressing NFATc1 suppresses chondrogenesis. Mechanistically, NFATc1 negatively regulated the transcriptional activity of the gene. Thus, our results reveal that NFATc1 characterizes articular, but not growth-plate, cartilage progenitors during development and negatively determines articular chondrocyte differentiation at least partly through regulating COL2A1 gene transcription.
Topics: Animals; Mice; Cartilage, Articular; Chondrocytes; NFATC Transcription Factors; Gene Expression Profiling; Cell Differentiation; Embryo, Mammalian
PubMed: 36790146
DOI: 10.7554/eLife.81569 -
Seminars in Musculoskeletal Radiology Jun 2020This article reviews implications for cartilage imaging in athletes in the setting of (1) acute chondral injury diagnosis, (2) evaluation and follow-up of conservative... (Review)
Review
This article reviews implications for cartilage imaging in athletes in the setting of (1) acute chondral injury diagnosis, (2) evaluation and follow-up of conservative and surgical therapy, and (3) evaluation of cartilage as a surrogate for meniscal function and joint stability. Focal knee cartilage defects are common in athletic populations. Athletes with articular cartilage injury may initially be able to return to sport with conservative therapy; however, a reduction of athletic ability and progression to osteoarthritis is expected in athletes with untreated severe chondral injury. For diagnostic and pre- and postsurgical evaluation purposes, morphological magnetic resonance (MR) assessment of the articular cartilage with high-resolution protocols is crucial. Although not widely implemented for clinical use, compositional MR techniques have great potential for monitoring the development and progression of biochemical and microstructural changes in cartilage extracellular matrix before gross morphological changes occur.
Topics: Athletic Injuries; Cartilage, Articular; Humans; Knee Injuries
PubMed: 32987423
DOI: 10.1055/s-0040-1708818 -
Seminars in Musculoskeletal Radiology Feb 2024Magnetic resonance imaging (MRI) has significantly advanced the understanding of osteoarthritis (OA) because it enables visualization of noncalcified tissues. Cartilage...
Magnetic resonance imaging (MRI) has significantly advanced the understanding of osteoarthritis (OA) because it enables visualization of noncalcified tissues. Cartilage is avascular and nurtured by diffusion, so it has a very low turnover and limited capabilities of repair. Consequently, prevention of structural and detection of premorphological damage is key in maintaining cartilage health. The integrity of cartilage composition and ultrastructure determines its mechanical properties but is not accessible to morphological imaging. Therefore, various techniques of compositional MRI with and without use of intravenous contrast medium have been developed. Spin-spin relaxation time (T2) and spin-lattice relaxation time constant in rotating frame (T1rho) mapping, the most studied cartilage biomarkers, were included in the recent standardization effort by the Quantitative Imaging Biomarkers Alliance (QIBA) that aims to make compositional MRI of cartilage clinically feasible and comparable. Additional techniques that are less frequently used include ultrashort echo time with T2*, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), glycosaminoglycan concentration by chemical exchange-dependent saturation transfer (gagCEST), sodium imaging, and diffusion-weighted MRI.
Topics: Humans; Cartilage, Articular; Contrast Media; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging; Biomarkers
PubMed: 38330968
DOI: 10.1055/s-0043-1776429 -
Experimental & Molecular Medicine Nov 2022The mitochondrial unfolded protein response (UPR) is a mitochondrial-to-nuclear signaling pathway that is activated to maintain mitochondrial function when there is an...
The mitochondrial unfolded protein response (UPR) is a mitochondrial-to-nuclear signaling pathway that is activated to maintain mitochondrial function when there is an accumulation of misfolded proteins within mitochondria. Mitochondrial function is essential for chondrocyte homeostasis, and mitochondrial dysfunction is a characteristic of osteoarthritis (OA). However, the role of the UPR in OA remains unclear. In the present study, the level of the UPR was examined in primary mouse chondrocytes subjected to different stresses and in the articular cartilage of OA model mice and OA patients. The relationship between UPR activation and OA progression was studied. The UPR was induced in primary mouse chondrocytes subjected to diverse stresses and in the cartilage of OA mice. Enhancement of the UPR with nicotinamide riboside (NR) significantly improved mitochondrial function, reduced chondrocyte death, attenuated OA pain, and ameliorated OA progression, and the protective effects decreased significantly in chondrocyte-specific Atf5 knockout (ATF5Col2a1-CreER) mice. UPR induction was also identified in the articular cartilage of OA patients and was associated with reduced chondrocyte death, less severe hip pain, and lower levels of inflammation in synovial fluid. These findings identify the induction of the UPR in primary mouse chondrocytes exposed to pathological stresses and in the articular cartilage of OA model mice and OA patients. Enhancement of the UPR ameliorates OA progression, suggesting that the UPR exerts a protective effect against OA and may be a potential diagnostic and therapeutic strategy for OA.
Topics: Mice; Animals; Unfolded Protein Response; Osteoarthritis; Chondrocytes; Cartilage, Articular; Pain
PubMed: 36380018
DOI: 10.1038/s12276-022-00885-y -
The Journal of Knee Surgery Jan 2021The return to play outcome is an important measure for orthopaedic sports medicine treatments. This variable is especially important when discussing cartilage treatments... (Review)
Review
The return to play outcome is an important measure for orthopaedic sports medicine treatments. This variable is especially important when discussing cartilage treatments because there are many different cartilage options available to athletes with articular injuries and this population is particularly interested in the ability to return to activities. Although many outcome variables are considered in any surgical procedure, the return-to-sport variable is focused on an active population and can be tailored to that patient's sport-specific goals. In this article, we will review some of the most recent and up-to-date articles describing return-to-sport outcomes for various knee cartilage treatments. This article will focus on the most common current knee cartilage treatments including microfracture, autologous chondrocyte implantation, osteochondral autograft transplant, and osteochondral allograft transplantation.
Topics: Arthroplasty, Subchondral; Athletic Injuries; Bone Transplantation; Cartilage, Articular; Chondrocytes; Humans; Intra-Articular Fractures; Knee Injuries; Knee Joint; Return to Sport; Transplantation, Autologous; Transplantation, Homologous
PubMed: 33389739
DOI: 10.1055/s-0040-1721669 -
Advances in Experimental Medicine and... 2023This chapter details how Alan Grodzinsky and his team unraveled the complex electromechanobiological structure-function relationships of articular cartilage and used...
This chapter details how Alan Grodzinsky and his team unraveled the complex electromechanobiological structure-function relationships of articular cartilage and used these insights to develop an impressively versatile shear and compression model. In this context, this chapter focuses (i) on the effects of mechanical compressive injury on multiple articular cartilage properties for (ii) better understanding the molecular concept of mechanical injury, by studying gene expression, signal transduction and the release of potential injury biomarkers. Furthermore, we detail how (iii) this was used to combine mechanical injury with cytokine exposure or co-culture systems for generating a more realistic trauma model to (iv) investigate the therapeutic modulation of the injurious response of articular cartilage. Impressively, Alan Grodzinsky's research has been and will remain to be instrumental in understanding the proinflammatory response to injury and in developing effective therapies that are based on an in-depth understanding of complex structure-function relationships that underlay articular cartilage function and degeneration.
Topics: Humans; Cartilage, Articular; Cartilage Diseases; Signal Transduction; Cytokines; Stress, Mechanical
PubMed: 37052850
DOI: 10.1007/978-3-031-25588-5_8 -
Connective Tissue Research Sep 2021Osteoarthritis is a common chronic disease of joints characterized by degenerative changes of articular cartilage. An early diagnosis of osteoarthritis may be possible...
Osteoarthritis is a common chronic disease of joints characterized by degenerative changes of articular cartilage. An early diagnosis of osteoarthritis may be possible when imaging excised tissue for research in situ at the cellular-molecular scale. Whereas cartilage histopathology is destructive, time-consuming, and limited to 2D views, contrast-enhanced x-ray microscopy (XRM) can image articular cartilage and subchondral bone in 3D. This study evaluates articular cartilage structure ex vivo using both techniques.Osteochondral plugs were excised from non-diseased bovine knees and stained in phosphotungstic acid for 0 to 32 h. XRM imaging revealed an optimal staining time of 16 h and a saturated staining time of 24 h. Histology sections were cut and analyzed by polarized light microscopy (PLM) and second-harmonic-generation dual-photon (SHG-DP) microscopy. Histology photomicrographs were aligned with matching XRM slices and evaluated for features relevant in histopathological scoring of osteoarthritis cartilage, including the tidemark, collagen architecture and chondrocyte morphology.The cartilage collagen network and chondrocytes from the 3D contrast-enhanced XRM were correlated with the 2D histology. This technique has two distinct advantages over routine histopathology: (1) the avoidance of dehydration, demineralization, and deformation of histological sectioning, thereby preserving the intact articular cartilage and subchondral bone plate ex vivo, and (2) the ability to evaluate the entire osteochondral volume in 3D. This work explores several diagnostic features of imaging cartilage, including: visualization of the tidemark in XRM and SHG-DP microscopy, validating the morphology of chondrocytes and nuclei with XRM, SHG-DP and PLM, and correlating collagen birefringence with XRM image intensity.
Topics: Animals; Cartilage, Articular; Cattle; Collagen; Microscopy; Osteoarthritis; X-Rays
PubMed: 32814448
DOI: 10.1080/03008207.2020.1813121 -
International Journal of Molecular... Dec 2019Osteoarthritis (OA) is a leading cause of disability and source of societal cost in older adults [...].
Osteoarthritis (OA) is a leading cause of disability and source of societal cost in older adults [...].
Topics: Animals; Biomarkers; Cartilage, Articular; Chondrocytes; Extracellular Matrix; Humans; Osteoarthritis
PubMed: 31817613
DOI: 10.3390/ijms20246156