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Acta Biochimica Et Biophysica Sinica Apr 2024Osteoarthritis (OA) is the most common joint disease, and good therapeutic results are often difficult to obtain due to its complex pathogenesis and diverse causative... (Review)
Review
Osteoarthritis (OA) is the most common joint disease, and good therapeutic results are often difficult to obtain due to its complex pathogenesis and diverse causative factors. After decades of research and exploration of OA, it has been progressively found that subchondral bone is essential for its pathogenesis, and pathological changes in subchondral bone can be observed even before cartilage lesions develop. Osteoclasts, the main cells regulating bone resorption, play a crucial role in the pathogenesis of subchondral bone. Subchondral osteoclasts regulate the homeostasis of subchondral bone through the secretion of degradative enzymes, immunomodulation, and cell signaling pathways. In OA, osteoclasts are overactivated by autophagy, ncRNAs, and Rankl/Rank/OPG signaling pathways. Excessive bone resorption disrupts the balance of bone remodeling, leading to increased subchondral bone loss, decreased bone mineral density and consequent structural damage to articular cartilage and joint pain. With increased understanding of bone biology and targeted therapies, researchers have found that the activity and function of subchondral osteoclasts are affected by multiple pathways. In this review, we summarize the roles and mechanisms of subchondral osteoclasts in OA, enumerate the latest advances in subchondral osteoclast-targeted therapy for OA, and look forward to the future trends of subchondral osteoclast-targeted therapies in clinical applications to fill the gaps in the current knowledge of OA treatment and to develop new therapeutic strategies.
Topics: Humans; Osteoclasts; Osteoarthritis; Bone Resorption; Bone Remodeling; Cartilage, Articular
PubMed: 38439665
DOI: 10.3724/abbs.2024017 -
BMC Musculoskeletal Disorders Jul 2023The weight-adjusted-waist Index (WWI), an innovative metric for assessing obesity, exhibits superior efficacy in appraising lean muscle and adipose tissue mass relative...
INTRODUCTION
The weight-adjusted-waist Index (WWI), an innovative metric for assessing obesity, exhibits superior efficacy in appraising lean muscle and adipose tissue mass relative to both the Body Mass Index (BMI) and Waist Circumference (WC). The objective of this research paper is to investigate the correlation between WWI and the incidence of Rheumatoid Arthritis (RA) and Osteoarthritis (OA).
METHODS
In this population-based study, we collected data from adult participants aged 20-80 years using the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2020 to analyze the association between WWI and the occurrence of RA and OA. NHANES, a nationally representative cross-sectional survey, is designed to evaluate the health and nutritional status of the U.S.
POPULATION
The current research incorporates an extensive, nationally representative sample of U.S. adults, utilizing weighted multivariate linear regression and smoothed curve fitting techniques to examine linear and non-linear relationships. Threshold effects were determined through a two-part linear regression model. Additionally, subgroup analyses and interaction tests were conducted to explore the connection between WWI and the incidence of RA and OA.
RESULTS
Our findings reveal a linear positive correlation between WWI and OA prevalence, indicating that an increase in WWI is linked to a heightened risk of OA. Conversely, a non-linear relationship was observed between WWI and RA prevalence, exhibiting a significant threshold effect with a saturation value of 11.21 cm/√kg. A positive association was detected to the left of the saturation point, while no significant association was present between the two variables to the right of the saturation point, suggesting a complex non-linear relationship between RA prevalence and WWI.
CONCLUSIONS
This investigation demonstrates a positive linear association between WWI and OA prevalence, as well as a complex non-linear relationship with RA prevalence in U.S. adults aged 20-80 years.
Topics: Adult; Humans; Nutrition Surveys; Prevalence; Cross-Sectional Studies; Osteoarthritis; Arthritis, Rheumatoid; Body Mass Index
PubMed: 37474953
DOI: 10.1186/s12891-023-06717-y -
Arthritis Research & Therapy Sep 2023Studies evaluating the association of knee and hip osteoarthritis (OA) with falls and fractures have inconsistent findings. We aimed to investigate associations of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Studies evaluating the association of knee and hip osteoarthritis (OA) with falls and fractures have inconsistent findings. We aimed to investigate associations of symptomatic and radiographic knee and hip OA with risk of falls, recurrent falls, and fractures.
METHODS
We conducted an electronic search of databases from inception to February 2023. Two authors independently screened studies, extracted data, and assessed the risk of bias using the Newcastle-Ottawa Scale tool in eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models.
RESULTS
Of 17 studies included (n = 862849), 2 had a high risk of bias. Among studies that evaluated falls or fractures as outcomes, 7/8 (87.5%) and 5/11 (45.5%) were self-reported, respectively. Both symptomatic knee and hip OA were associated with increased risk of recurrent falls (knee: OR = 1.55, 95% CI 1.10 to 2.18; hip: OR = 1.50, 95% CI 1.28 to 1.75) but not falls or fractures. Radiographic knee OA increased risk of falls (OR = 1.28, 95% CI 1.03 to 1.59) and did not significantly increase risk of recurrent falls (OR = 1.39, 95% CI 0.97 to 1.97) or fractures (OR = 1.22, 95% CI 0.99 to 1.52). Radiographic hip OA decreased the risk of recurrent falls (OR = 0.70, 95% CI 0.51 to 0.96) but had no statistically significant association with fractures (OR = 1.16, 95% CI 0.79 to 1.71).
CONCLUSION
Symptomatic knee and hip OA were both associated with an increased risk of recurrent falls, and radiographic knee OA was associated with an increased risk of falls. No statistically significant associations of radiographic and symptomatic knee or hip OA with fractures were found.
Topics: Humans; Osteoarthritis, Hip; Accidental Falls; Risk Factors; Fractures, Bone; Osteoarthritis, Knee
PubMed: 37770969
DOI: 10.1186/s13075-023-03179-4 -
Advanced Science (Weinheim,... Feb 2024Destruction of cartilage due to the abnormal remodeling of subchondral bone (SB) leads to osteoarthritis (OA), and restoring chondro-bone metabolic homeostasis is the...
Destruction of cartilage due to the abnormal remodeling of subchondral bone (SB) leads to osteoarthritis (OA), and restoring chondro-bone metabolic homeostasis is the key to the treatment of OA. However, traditional intra-articular injections for the treatment of OA cannot directly break through the cartilage barrier to reach SB. In this study, the hydrothermal method is used to synthesize ultra-small size (≈5 nm) selenium-doped carbon quantum dots (Se-CQDs, SC), which conjugated with triphenylphosphine (TPP) to create TPP-Se-CQDs (SCT). Further, SCT is dynamically complexed with hyaluronic acid modified with aldehyde and methacrylic anhydride (AHAMA) to construct highly permeable micro/nano hydrogel microspheres (SCT@AHAMA) for restoring chondro-bone metabolic homeostasis. In vitro experiments confirmed that the selenium atoms scavenged reactive oxygen species (ROS) from the mitochondria of mononuclear macrophages, inhibited osteoclast differentiation and function, and suppressed early chondrocyte apoptosis to maintain a balance between cartilage matrix synthesis and catabolism. In vivo experiments further demonstrated that the delivery system inhibited osteoclastogenesis and H-vessel invasion, thereby regulating the initiation and process of abnormal bone remodeling and inhibiting cartilage degeneration in SB. In conclusion, the micro/nano hydrogel microspheres based on ultra-small quantum dots facilitate the efficient penetration of articular SB and regulate chondro-bone metabolism for OA treatment.
Topics: Humans; Microspheres; Hydrogels; Selenium; Cartilage, Articular; Osteoarthritis
PubMed: 38084002
DOI: 10.1002/advs.202305023 -
RMD Open Dec 2023The pathogenesis of hand osteoarthritis (OA) remains unknown. Hyperuricaemia, which is related to inflammation, may play a role in hand OA, but evidence is lacking. In a... (Observational Study)
Observational Study
OBJECTIVE
The pathogenesis of hand osteoarthritis (OA) remains unknown. Hyperuricaemia, which is related to inflammation, may play a role in hand OA, but evidence is lacking. In a large population-based study, we examined the association between hyperuricaemia and hand OA.
METHODS
Participants were from the Xiangya OA Study, a community-based observational study. Hyperuricaemia was defined as serum urate >416 µmol/L in men and >357 µmol/L in women. Radiographic hand OA (RHOA) was defined as presence of the modified Kellgren-Lawrence grade ≥2 in any hand joint. Symptomatic hand OA (SHOA) was defined as presence of both self-reported symptoms and RHOA in the same hand. The associations of hyperuricaemia with RHOA or SHOA were examined using generalised estimating equations.
RESULTS
Among 3628 participants, the prevalence of RHOA was higher in participants with hyperuricaemia than those with normouricaemia (26.9% vs 20.9%), with an adjusted OR (aOR) of 1.34 (95% CI 1.11 to 1.61). The associations were consistent in men (aOR 1.33, 95% CI 1.01 to 1.74) and women (aOR 1.35, 95% CI 1.05 to 1.74). Hyperuricaemia was mainly associated with bilateral RHOA (aOR 1.54, 95% CI 1.18 to 2.01) but not unilateral RHOA (aOR 1.13, 95% CI 0.89 to 1.45). Prevalence of SHOA was higher, although statistically insignificant, in participants with hyperuricaemia (aOR 1.39, 95% CI 0.94 to 2.07).
CONCLUSION
In this population-based study, hyperuricaemia was associated with a higher prevalence of hand OA. Future prospective studies are required to investigate the temporal relationship.
TRIAL REGISTRATION NUMBER
NCT04033757.
Topics: Male; Humans; Female; Hyperuricemia; Osteoarthritis; Hand Joints; Hand; Prospective Studies
PubMed: 38053456
DOI: 10.1136/rmdopen-2023-003683 -
Journal of Extracellular Vesicles Jul 2023Human small extracellular vesicles (sEVs) derived from adipose-derived mesenchymal stromal cells (ASC) have been reported to suppress the progression of osteoarthritis...
Small extracellular vesicles derived from human adipose-derived mesenchymal stromal cells cultured in a new chemically-defined contaminate-free media exhibit enhanced biological and therapeutic effects on human chondrocytes in vitro and in a mouse osteoarthritis model.
Human small extracellular vesicles (sEVs) derived from adipose-derived mesenchymal stromal cells (ASC) have been reported to suppress the progression of osteoarthritis (OA) in animal studies and subsequently, translation of this potential to assess their clinical efficacy is anticipated. However, fabrication protocols for sEVs to eliminate potential contamination by culture medium-derived components need to be established prior to their clinical use. The purpose of the present studies was to elucidate the influence of medium-derived contaminants on the biological effects of sEVs, and to establish isolation methods for sEVs using a new clinical grade chemically-defined media (CDM). The quantity and purity of ASC-derived sEVs cultured in four different CDMs (CDM1, 2, 3 and 4) were evaluated. The concentrates of the four media incubated without cells were used as the background (BG) control for each set of sEVs. The biological effect of sEVs fabricated in the four different CDMs on normal human articular chondrocytes (hACs) were evaluated in vitro using a variety of methodological assessments. Finally, the sEVs with the highest purity were tested for their ability to suppress the progression of knee OA mouse model. Analysis of the BG controls revealed that CDM1-3 contained detectable particles, while there was no visible contamination of culture media-derived components detected with CDM4. Accordingly, the sEVs fabricated with CDM4 (CDM4-sEVs) exhibited the highest purity and yield. Notably, the CDM4-sEVs were the most efficient in promoting the cellular proliferation, migration, chondrogenic differentiation, and anti-apoptotic activity of hACs. Furthermore, CDM4-sEVs significantly suppressed the osteochondral degeneration in vivo model. Small EVs derived from ASCs cultured in a CDM without detectable contaminants demonstrated enhanced biological effects on hACs and the progression of OA. Thus, sEVs isolated with CDM4 most optimally meet the requirements of efficacy and safety for assessment in their future clinical applications.
Topics: Animals; Mice; Humans; Chondrocytes; Extracellular Vesicles; Mesenchymal Stem Cells; Osteoarthritis; Disease Models, Animal
PubMed: 37367299
DOI: 10.1002/jev2.12337 -
Ageing Research Reviews Jul 2024Alzheimer's disease (AD) is the most common type of cognitive impairment. AD is closely related to orthopedic diseases, such as osteoporosis and osteoarthritis, in terms... (Review)
Review
Alzheimer's disease (AD) is the most common type of cognitive impairment. AD is closely related to orthopedic diseases, such as osteoporosis and osteoarthritis, in terms of epidemiology and pathogenesis. Brain and bone tissues can regulate each other in different manners through bone-brain axis. This article reviews the research progress of the relationship between AD and orthopedic diseases, bone-brain axis mechanisms of AD, and AD therapy by targeting bone-brain axis, in order to deepen the understanding of bone-brain communication, promote early diagnosis and explore new therapy for AD patients.
Topics: Alzheimer Disease; Humans; Brain; Bone and Bones; Animals; Osteoporosis; Osteoarthritis
PubMed: 38759893
DOI: 10.1016/j.arr.2024.102341 -
The Lancet. Rheumatology Jul 2023Many international clinical guidelines recommend therapeutic exercise as a core treatment for knee and hip osteoarthritis. We aimed to identify individual patient-level... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many international clinical guidelines recommend therapeutic exercise as a core treatment for knee and hip osteoarthritis. We aimed to identify individual patient-level moderators of the effect of therapeutic exercise for reducing pain and improving physical function in people with knee osteoarthritis, hip osteoarthritis, or both.
METHODS
We did a systematic review and individual participant data (IPD) meta-analysis of randomised controlled trials comparing therapeutic exercise with non-exercise controls in people with knee osteoathritis, hip osteoarthritis, or both. We searched ten databases from March 1, 2012, to Feb 25, 2019, for randomised controlled trials comparing the effects of exercise with non-exercise or other exercise controls on pain and physical function outcomes among people with knee osteoarthritis, hip osteoarthritis, or both. IPD were requested from leads of all eligible randomised controlled trials. 12 potential moderators of interest were explored to ascertain whether they were associated with short-term (12 weeks), medium-term (6 months), and long-term (12 months) effects of exercise on self-reported pain and physical function, in comparison with non-exercise controls. Overall intervention effects were also summarised. This study is prospectively registered on PROSPERO (CRD42017054049).
FINDINGS
Of 91 eligible randomised controlled trials that compared exercise with non-exercise controls, IPD from 31 randomised controlled trials (n=4241 participants) were included in the meta-analysis. Randomised controlled trials included participants with knee osteoarthritis (18 [58%] of 31 trials), hip osteoarthritis (six [19%]), or both (seven [23%]) and tested heterogeneous exercise interventions versus heterogeneous non-exercise controls, with variable risk of bias. Summary meta-analysis results showed that, on average, compared with non-exercise controls, therapeutic exercise reduced pain on a standardised 0-100 scale (with 100 corresponding to worst pain), with a difference of -6·36 points (95% CI -8·45 to -4·27, borrowing of strength [BoS] 10·3%, between-study variance [τ] 21·6) in the short term, -3·77 points (-5·97 to -1·57, BoS 30·0%, τ 14·4) in the medium term, and -3·43 points (-5·18 to -1·69, BoS 31·7%, τ 4·5) in the long term. Therapeutic exercise also improved physical function on a standardised 0-100 scale (with 100 corresponding to worst physical function), with a difference of -4·46 points in the short term (95% CI -5·95 to -2·98, BoS 10·5%, τ 10·1), -2·71 points in the medium term (-4·63 to -0·78, BoS 33·6%, τ 11·9), and -3·39 points in the long term (-4·97 to -1·81, BoS 34·1%, τ 6·4). Baseline pain and physical function moderated the effect of exercise on pain and physical function outcomes. Those with higher self-reported pain and physical function scores at baseline (ie, poorer physical function) generally benefited more than those with lower self-reported pain and physical function scores at baseline, with the evidence most certain in the short term (12 weeks).
INTERPRETATION
There was evidence of a small, positive overall effect of therapeutic exercise on pain and physical function compared with non-exercise controls. However, this effect is of questionable clinical importance, particularly in the medium and long term. As individuals with higher pain severity and poorer physical function at baseline benefited more than those with lower pain severity and better physical function at baseline, targeting individuals with higher levels of osteoarthritis-related pain and disability for therapeutic exercise might be of merit.
FUNDING
Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health and Care Research.
Topics: Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Knee Joint; Exercise Therapy; Pain
PubMed: 38251550
DOI: 10.1016/S2665-9913(23)00122-4 -
Frontiers in Immunology 2023Osteoarthritis (OA) is the most frequent musculoskeletal disease and the major contributor to disability worldwide. Metabolic syndrome (MetS) has been recognized as...
BACKGROUND
Osteoarthritis (OA) is the most frequent musculoskeletal disease and the major contributor to disability worldwide. Metabolic syndrome (MetS) has been recognized as being associated with the pathogenesis of osteoarthritis. However, the exact mechanisms and links between the two are not clear.
METHODS
We downloaded clinical information data and gene expression profiles for OA and MetS from the database of Gene Expression Omnibus (GEO), and immune related gene (IRG) from the database of Immunology Database and Analysis Portal (IMMPORT). After screening OA-DEG and MetS-DEG, we identified the common immune hub gene by screening the overlapping genes between OA-DEG, MetS-DEG and IRG. Then we conducted single-gene analysis of S100A8, assessed the correlation of S100A8 with immune cell infiltration, and verified the diagnostic value of S100A8 in OA and MetS database respectively.
RESULTS
323 OA-DEGs,101 MetS-DEGs and an immune-related hub gene, S100A8, were identified. In single gene analysis of S100A8 in OA samples, GSEA suggested that immune-related biological processes were more significantly enriched. The results of immune cell infiltration analysis showed that the enrichment fraction of M2 macrophages was significantly higher in the high S100A8-expressing group, and the level of S100A8 expression was positively correlated with M2 macrophage infiltration. The results of the dataset validation showed that S100A8 expression levels were significantly upregulated in the OA group and performed well in the diagnosis of OA. In single gene analysis of S100A8 in MetS samples, immune cell infiltration analysis showed that monocyte infiltration was higher in the S100A8 high expression samples and that there was a positive correlation between the two. Dataset validation showed that S100A8 is of high value for the diagnosis of MetS. In the validation of the dataset for the four metabolism-related diseases (obesity, diabetes, hypertension and hyperlipidaemia), S100A8 was expressed at higher levels in the disease group and also had a higher diagnostic value for the four metabolism-related diseases.
CONCLUSION
S100A8 is a common hub gene and diagnostic biomarker for OA and MetS, and the immune regulation involved in S100A8 may play a central role in the pathogenesis of OA and MetS.
Topics: Humans; Biomarkers; Calgranulin A; Metabolic Syndrome; Musculoskeletal Diseases; Obesity; Osteoarthritis
PubMed: 37497233
DOI: 10.3389/fimmu.2023.1185275 -
Nutrients Sep 2023(1) Many studies have attempted to utilize metabolomic approaches to explore potential biomarkers for the early detection of osteoarthritis (OA), but consistent and... (Meta-Analysis)
Meta-Analysis Review
(1) Many studies have attempted to utilize metabolomic approaches to explore potential biomarkers for the early detection of osteoarthritis (OA), but consistent and high-level evidence is still lacking. In this study, we performed a systematic review and meta-analysis of differential small molecule metabolites between OA patients and healthy individuals to screen promising candidates from a large number of samples with the aim of informing future prospective studies. (2) Methods: We searched the EMBASE, the Cochrane Library, PubMed, Web of Science, Wan Fang Data, VIP Date, and CNKI up to 11 August 2022, and selected relevant records based on inclusion criteria. The risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. We performed qualitative synthesis by counting the frequencies of changing directions and conducted meta-analyses using the random effects model and the fixed-effects model to calculate the mean difference and 95% confidence interval. (3) Results: A total of 3798 records were identified and 13 studies with 495 participants were included. In the 13 studies, 132 kinds of small molecule differential metabolites were extracted, 58 increased, 57 decreased and 17 had direction conflicts. Among them, 37 metabolites appeared more than twice. The results of meta-analyses among four studies showed that three metabolites increased, and eight metabolites decreased compared to healthy controls (HC). (4) Conclusions: The main differential metabolites between OA and healthy subjects were amino acids (AAs) and their derivatives, including tryptophan, lysine, leucine, proline, phenylalanine, glutamine, dimethylglycine, citrulline, asparagine, acetylcarnitine and creatinine (muscle metabolic products), which could be potential biomarkers for predicting OA.
Topics: Humans; Prospective Studies; Osteoarthritis; Biomarkers; Bias; Health Status
PubMed: 37836475
DOI: 10.3390/nu15194191