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Molecules (Basel, Switzerland) Mar 2024Osteoarthritis (OA) is a chronic joint disease that causes pathological changes in articular cartilage, synovial membrane, or subchondral bone. Conventional treatments... (Review)
Review
Osteoarthritis (OA) is a chronic joint disease that causes pathological changes in articular cartilage, synovial membrane, or subchondral bone. Conventional treatments for OA include surgical and non-surgical methods. Surgical treatment is suitable for patients in the terminal stage of OA. It is often the last choice because of the associated risks and high cost. Medication of OA mainly includes non-steroidal anti-inflammatory drugs, analgesics, hyaluronic acid, and cortico-steroid anti-inflammatory drugs. However, these drugs often have severe side effects and cannot meet the needs of patients. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Apoptosis is programmed cell death, which is a kind of physiologic cell suicide determined by heredity and conserved by evolution. Inhibition of apoptosis-related pathways has been found to prevent and treat a variety of diseases. Excessive apoptosis can destroy cartilage homeostasis and aggravate the pathological process of OA. Therefore, inhibition of apoptosis-related factors or signaling pathways has become an effective means to treat OA. Phytochemicals are active ingredients from plants, and it has been found that phytochemicals can play an important role in the prevention and treatment of OA by inhibiting apoptosis. We summarize preclinical and clinical studies of phytochemicals for the treatment of OA by inhibiting apoptosis. The results show that phytochemicals can treat OA by targeting apoptosis-related pathways. On the basis of improving some phytochemicals with low bioavailability, poor water solubility, and high toxicity by nanotechnology-based drug delivery systems, and at the same time undergoing strict clinical and pharmacological tests, phytochemicals can be used as a potential therapeutic drug for OA and may be applied in clinical settings.
Topics: Humans; Osteoarthritis; Phytochemicals; Apoptosis; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability
PubMed: 38611766
DOI: 10.3390/molecules29071487 -
Skeletal Radiology Nov 2023Magnetic resonance imaging (MRI) is widely regarded as the primary modality for the morphological assessment of cartilage and all other joint tissues involved in... (Review)
Review
Magnetic resonance imaging (MRI) is widely regarded as the primary modality for the morphological assessment of cartilage and all other joint tissues involved in osteoarthritis. 2D fast spin echo fat-suppressed intermediate-weighted (FSE FS IW) sequences with a TE between 30 and 40ms have stood the test of time and are considered the cornerstone of MRI protocols for clinical practice and trials. These sequences offer a good balance between sensitivity and specificity and provide appropriate contrast and signal within the cartilage as well as between cartilage, articular fluid, and subchondral bone. Additionally, FS IW sequences enable the evaluation of menisci, ligaments, synovitis/effusion, and bone marrow edema-like signal changes. This review article provides a rationale for the use of FSE FS IW sequences in the morphological assessment of cartilage and osteoarthritis, along with a brief overview of other clinically available sequences for this indication. Additionally, the article highlights ongoing research efforts aimed at improving FSE FS IW sequences through 3D acquisitions with enhanced resolution, shortened examination times, and exploring the potential benefits of different magnetic field strengths. While most of the literature on cartilage imaging focuses on the knee, the concepts presented here are applicable to all joints. KEY POINTS: 1. MRI is currently considered the modality of reference for a "whole-joint" morphological assessment of osteoarthritis. 2. Fat-suppressed intermediate-weighted sequences remain the keystone of MRI protocols for the assessment of cartilage morphology, as well as other structures involved in osteoarthritis. 3. Trends for further development in the field of cartilage and joint imaging include 3D FSE imaging, faster acquisition including AI-based acceleration, and synthetic imaging providing multi-contrast sequences.
Topics: Humans; Cartilage, Articular; Knee Joint; Knee; Imaging, Three-Dimensional; Osteoarthritis; Magnetic Resonance Imaging
PubMed: 37154871
DOI: 10.1007/s00256-023-04343-2 -
Journal of Physical Activity & Health Aug 2023The objectives were (1) to establish the strength of the association between incident cases of osteoarthritis (OA) and low back pain (LBP), and physical activity (PA)... (Review)
Review
OBJECTIVE
The objectives were (1) to establish the strength of the association between incident cases of osteoarthritis (OA) and low back pain (LBP), and physical activity (PA) and to assess the likelihood of the associations being causal; and (2) to quantify the impact of PA on the burden of OA and LBP in Australia.
METHODS
We conducted a systematic literature review in EMBASE and PubMed databases from January 01, 2000, to April 28, 2020. We used the Bradford Hill viewpoints to assess causality. We used a proportional multistate life table model to estimate the impact of changes in the PA levels on OA and LBP burdens for the 2019 Australian population (aged ≥ 20 y) over their remaining lifetime.
RESULTS
We found that both OA and LBP are possibly causally related to physical inactivity. Assuming causality, our model projected that if the 2025 World Health Organization global target for PA was met, the burden in 25 years' time could be reduced by 70,000 prevalent cases of OA and over 11,000 cases of LBP. Over the lifetime of the current adult population of Australia, the gains could add up to approximately 672,814 health-adjusted life years (HALYs) for OA (ie, 27 HALYs per 1000 persons) and 114,042 HALYs for LBP (ie, 5 HALYs per 1000 persons). The HALY gains would be 1.4 times bigger if the 2030 World Health Organization global target for PA was achieved and 11 times bigger if all Australians adhered to the Australian PA guidelines.
CONCLUSION
This study provides empirical support for the adoption of PA in strategies for the prevention of OA and back pain.
Topics: Adult; Humans; Exercise; Life Tables; Low Back Pain; Occupational Diseases; Australia; Osteoarthritis
PubMed: 37268300
DOI: 10.1123/jpah.2022-0541 -
Arthritis Research & Therapy Jul 2023Neck pain (NP) is a common symptom reported in the elderly. However, no study has examined the relationship between NP and osteoarthritis (OA) so far, and this study...
BACKGROUND
Neck pain (NP) is a common symptom reported in the elderly. However, no study has examined the relationship between NP and osteoarthritis (OA) so far, and this study aimed to investigate the association of neck pain with the prevalence and mortality of OA.
METHODS
A total of 5965 participants were included in this cohort study based on the National Health and Nutrition Examination Survey data set of the USA (NHANES). Death outcomes follow-up information was ascertained by linkage to National Death Index (NDI). The association between NP and OA was studied by multi-various logistic regression models after adjusting for potential confounding factors. Cox proportional hazards models were used to elucidate the relationship between NP and all-cause mortality in OA patients.
RESULTS
Among all participants, 8.18% had osteoarthritis, and 5.92% suffered from neck pain. Neck pain was associated with osteoarthritis [1.932 (1.232, 3.028), p < 0.01], which still reminded significant after adjustments [2.519 (1.325, 4.788), p < 0.01] and stratified analysis by sex, race, and smoke status. In OA patients, chronic neck pain (over 1 year) was significantly associated with higher risks of all-cause mortality before [2.94 (1.61, 5.37), p < 0.01] and after adjustment [3.30 (1.23, 45.85), p < 0.05].
CONCLUSION
Neck pain was strongly associated with osteoarthritis. Moreover, chronic neck pain over 1 year significantly increased the mortality of OA patients. Our study demonstrates the need to screen osteoarthritis in the neck pain population and select a more appropriate treatment strategy promptly for those patients.
Topics: Humans; Aged; Cohort Studies; Nutrition Surveys; Neck Pain; Prospective Studies; Osteoarthritis; Chronic Pain; Osteoarthritis, Knee
PubMed: 37468971
DOI: 10.1186/s13075-023-03103-w -
Plasma lipids, alcohol intake frequency and risk of Osteoarthritis: a Mendelian randomization study.BMC Public Health Jul 2023Plasma lipids and alcohol intake frequency have been reported to be associated with the risk of osteoarthritis (OA). However, it remains inconclusive whether plasma...
BACKGROUD
Plasma lipids and alcohol intake frequency have been reported to be associated with the risk of osteoarthritis (OA). However, it remains inconclusive whether plasma lipids and alcohol intake frequency play a role in the development of OA.
METHODS
The study employed a comprehensive genome-wide association database to identify independent genetic loci strongly linked to plasma lipids and alcohol intake frequency, which were used as instrumental variables. The causal association between plasma lipids, alcohol intake frequency, and the risk of OA was then analyzed using two-sample Mendelian randomization methods such as inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), with odds ratios (ORs) as the evaluation criteria.
RESULTS
A total of 392 SNPs were included as instrumental variables in this study, including 32 for total cholesterol (TC), 39 for triglycerides (TG), 170 for high-density lipoproteins (HDL), 60 for low-density lipoproteins (LDL), and 91 for alcohol intake frequency. Using the above two-sample Mendelian Randomization method to derive the causal association between exposure and outcome, with the IVW method as the primary analysis method and other MR analysis methods complementing IVW. The results of this study showed that four exposure factors were causally associated with the risk of OA. TC obtained a statistically significant result for IVW (OR = 1.207, 95% CI: 1.018-1.431, P = 0.031); TG obtained a statistically significant result for Simple mode (OR = 1.855, 95% CI: 1.107-3.109, P = 0.024); LDL obtained three statistically significant results for IVW, WME and Weighted mode (IVW: OR = 1.363, 95% CI: 1.043-1.781, P = 0.023; WME: OR = 1.583, 95% CI: 1.088-2.303, P = 0.016; Weighted mode: OR = 1.521, 95% CI: 1.062-2.178, P = 0.026). Three statistically significant results were obtained for alcohol intake frequency with IVW, WME and Weighted mode (IVW: OR = 1.326, 95% CI: 1.047-1.678, P = 0.019; WME: OR = 1.477, 95% CI: 1.059-2.061, P = 0.022; Weighted mode: OR = 1.641, 95% CI: 1.060-2.541, P = 0.029). TC, TG, LDL, and alcohol intake frequency were all considered as risk factors for OA. The Cochran Q test for the IVW and MR-Egger methods indicated intergenic heterogeneity in the SNPs contained in TG, HDL, LDL, and alcohol intake frequency, and the test for pleiotropy indicated a weak likelihood of pleiotropy in all causal analyses.
CONCLUSIONS
The results of two-sample Mendelian randomization analysis showed that TC, TG, LDL, and alcohol intake frequency were risk factors for OA, and the risk of OA increased with their rise.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Alcohol Drinking; Risk Factors; Osteoarthritis; Triglycerides; Lipoproteins, HDL
PubMed: 37434151
DOI: 10.1186/s12889-023-16250-1 -
Skeletal Radiology Nov 2023Traditionally, osteoarthritis (OA) is diagnosed with the clinical examination supplemented by the conventional radiography (CR). In the research literature, the role of... (Review)
Review
Traditionally, osteoarthritis (OA) is diagnosed with the clinical examination supplemented by the conventional radiography (CR). In the research literature, the role of ultrasound (US) imaging in the diagnostics of OA has risen steadily during the last two decades. US imaging is cheap and globally widely available often already in primary healthcare. Here, we reviewed the most essential US literature focusing on OA diagnostics and progression prediction using the various search engines. Starting from the year 2000, our search provided 1 445 journal articles. After reviewing the abstracts, 89 articles were finally included. Most of the reviewed articles focused on the imaging of knee and hand OA, whereas only a minority dealt with the imaging of hip, ankle, midfoot, acromioclavicular, and temporomandibular joints. Overall, during the last 20 years, the use of US imaging for OA assessment has increased in the scientific literature. In knee and hand joints, US imaging has been reported to be a promising tool to evaluate OA changes. Furthermore, the reproducibility of US as well as its association to MRI findings are excellent. Importantly, US seems to even outperform CR in certain aspects, such as detection of osteophytes, joint inflammation, meniscus protrusion, and localized cartilage damage (especially at the medial femoral condyle and sulcus area). Based on the reviewed literature, US can be truly considered as a complementary tool to CR in the clinical setup for OA diagnostics. New technical developments may even enhance the diagnostic value of the US in the future.
Topics: Humans; Reproducibility of Results; Osteoarthritis; Ultrasonography; Knee Joint; Radiography; Magnetic Resonance Imaging; Osteoarthritis, Knee
PubMed: 37060461
DOI: 10.1007/s00256-023-04342-3 -
Free Radical Biology & Medicine Feb 2024Ferroptosis is involved in the pathogenesis of osteoarthritis (OA) while suppression of chondrocyte ferroptosis has a beneficial effect on OA. However, the molecular...
Ferroptosis is involved in the pathogenesis of osteoarthritis (OA) while suppression of chondrocyte ferroptosis has a beneficial effect on OA. However, the molecular mechanism of ferroptosis in OA remains to be elucidated. P21, an indicator of aging, has been reported to inhibit ferroptosis, but the relationship between P21 and ferroptosis in OA remains unclear. Here, we aimed to investigate the expression and function of P21 in OA chondrocytes, and the involvement of P21 in the regulation of ferroptosis in chondrocytes. First, we demonstrated that high P21 expression was observed in the cartilage from OA patients and destabilized medial meniscus (DMM) mice, and in osteoarthritic chondrocytes induced by IL-1β, FAC and erastin. P21 knockdown exacerbated the reduction of Col2a1 and promoted the upregulation of MMP13 in osteoarthritic chondrocytes. Meanwhile, P21 knockdown exacerbated cartilage degradation in DMM-induced OA mouse models and decreased GPX4 expression in vivo. Furthermore, P21 knockdown sensitized chondrocytes to ferroptosis induced by erastin, which was closely associated with the accumulation of lipid peroxides. In mechanism, we demonstrated that P21 regulated the stability of GPX4 protein, and the regulation was independent of NRF2. Meanwhile, we found that P21 significantly affected the recruitment of GPX4 to linear ubiquitin chain assembly complex (LUBAC) and regulated the level of M1-linked ubiquitination of GPX4. Overall, our results suggest that P21 plays an essential anti-ferroptosis role in OA by regulating the stability of GPX4.
Topics: Humans; Mice; Animals; Chondrocytes; Ferroptosis; Cartilage; Disease Models, Animal; Up-Regulation; Osteoarthritis
PubMed: 38176476
DOI: 10.1016/j.freeradbiomed.2023.12.047 -
Molecular Therapy : the Journal of the... May 2024Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory...
Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory mechanisms of which remain elusive. This study identifies the essential role of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in maintaining articular cartilage homeostasis. Hnrnpk expression is markedly downregulated in human and mice OA cartilage. The deletion of Hnrnpk effectively accelerates the development of post-traumatic and age-dependent OA in mice. Mechanistically, the KH1 and KH2 domain of Hnrnpk bind and degrade the mRNA of WWC1. Hnrnpk deletion increases WWC1 expression, which in turn leads to the activation of Hippo signaling and ultimately aggravates OA. In particular, intra-articular injection of LPA and adeno-associated virus serotype 5 expressing WWC1 RNA interference ameliorates cartilage degeneration induced by Hnrnpk deletion, and intra-articular injection of adeno-associated virus serotype 5 expressing Hnrnpk protects against OA. Collectively, this study reveals the critical roles of Hnrnpk in inhibiting OA development through WWC1-dependent downregulation of Hippo signaling in chondrocytes and defines a potential target for the prevention and treatment of OA.
Topics: Animals; Humans; Male; Mice; Cartilage, Articular; Chondrocytes; Dependovirus; Disease Models, Animal; Gene Expression Regulation; Heterogeneous-Nuclear Ribonucleoprotein K; Hippo Signaling Pathway; Intracellular Signaling Peptides and Proteins; Osteoarthritis; Protein Serine-Threonine Kinases; RNA, Messenger; Signal Transduction
PubMed: 38414246
DOI: 10.1016/j.ymthe.2024.02.027 -
Scientific Reports Oct 2023Osteoarthritis (OA), a degenerative disease of the joints, has one of the highest disability rates worldwide. This study investigates the role of pyroptosis-related...
Osteoarthritis (OA), a degenerative disease of the joints, has one of the highest disability rates worldwide. This study investigates the role of pyroptosis-related genes in osteoarthritis and their expression in different chondrocyte subtypes at the individual cell level. Using OA-related datasets for single-cell RNA sequencing and RNA-seq, the study identified PRDEGs and DEGs and conducted Cox regression analysis to identify independent prognostic factors for OA. CASP6, NOD1, and PYCARD were found to be prognostic factors. Combined Weighted Gene Correlation Network Analysis with PPI network, a total of 15 hub genes related to pyroptosis were involved in the notch and oxidative phosphorylation pathways, which could serve as biomarkers for the diagnosis and prognosis of OA patients. The study also explored the heterogeneity of chondrocytes between OA and normal samples, identifying 19 single-cell subpopulation marker genes that were significantly different among 7 chondrocyte cell clusters. AGT, CTSD, CYBC, and THYS1 were expressed differentially among different cell subpopulations, which were associated with cartilage development and metabolism. These findings provide valuable insights into the molecular mechanisms underlying OA and could facilitate the development of new therapeutic strategies for this debilitating disease.
Topics: Humans; Gene Expression Profiling; Gene Expression Regulation; Pyroptosis; Osteoarthritis; Chondrocytes; Prognosis; Sequence Analysis, RNA
PubMed: 37853066
DOI: 10.1038/s41598-023-44724-0 -
Theranostics 2023Enzymes are central components of many physiological processes, and changes in enzyme activity are linked to numerous disease states, including osteoarthritis (OA)....
Enzymes are central components of many physiological processes, and changes in enzyme activity are linked to numerous disease states, including osteoarthritis (OA). Assessing changes in enzyme function can be challenging because of difficulties in separating affected tissue areas that result in the homogenisation of healthy and diseased cells. Direct correlation between spatially-resolved enzyme distribution(s) and diseased cells/tissues can thus lead to advances in our understanding of OA pathophysiology. Herein, we present a method that uses mass spectrometry imaging (MSI) to visualise the distribution of lipase enzymes and their downstream lipid products in fresh bone and cartilage tissue sections. Immunohistostaining of adjacent tissue sections was then used to identify OA cells/tissues, which were then statistically correlated with molecular-level images. MSI was used to image lipase enzymes, their substrates, and their metabolic products to validate enzymatic activity and correlate to OA regions determined by immunohistochemistry (IHC). Based on the modified Mankin score, six non-OA and OA patient-matched osteochondral samples were analysed by matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI). Due to the involvement of phospholipase A2 (PLA) in inflammatory pathways, explant tissues were treated with IL-1β to mimic inflammation observed in OA. Bovine explant tissues were then subject to MSI methods to observe the spatial distribution of PLA. Compared with non-OA samples, OA samples showed an elevated level of multiple arachidonic acid (AA)-containing phospholipids ( < 0.001), in which the elevation in the surface and deep layer cartilage of OA tissues is correlated to elevated PLA activity ( < 0.001). Bovine explant tissues treated with IL-1β to mimic OA pathophysiology validated these results and displayed elevated PLA levels in OA mimic samples relative to the controls ( < 0.001). It was established that the PLAGA isoform specifically was responsible for PLA enzyme activity changes in OA tissues ( < 0.001). Our results present a reliable method for imaging enzyme dynamics in OA cartilage, which sets up the foundation for future spatial enzyme dynamics in the OA field. We demonstrated that OA patients exhibit increased expression of PLAGA at the superficial and deep cartilage zone that degrades cartilage differently at the spatial level. A tissue-specific PLAGA precision inhibition may be the potential target for OA.
Topics: Humans; Animals; Cattle; Osteoarthritis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Inflammation; Lipase; Polyesters
PubMed: 37649605
DOI: 10.7150/thno.86623