Connective Tissue Research最新文献

{"title":"Post-injury tendon mechanics are not affected by tamoxifen treatment.","authors":"Zakary M Beach, Ashley K Fung, Stephanie N Weiss, Louis J Soslowsky","doi":"10.1080/03008207.2022.2097907","DOIUrl":"10.1080/03008207.2022.2097907","url":null,"abstract":"<p><strong>Purpose: </strong>A growing interest in the mechanisms that govern tendon healing has resulted in the develop-ment of tools, such as the tamoxifen-inducible mouse knockdown model, to address these questions. However, tamoxifen is a selective estrogen receptor modulator and may interfere with the tendon healing process. The objective of this study was to evaluate the effects of tamoxifen on post-injury tendon mechanics in wild-type mice.</p><p><strong>Methods: </strong>The mice underwent treatment at the time of injury using an established mouse injury model and the injured tendons were evaluated 3 weeks post-injury. The treatment contained tamoxifen suspended in corn oil and was compared to a treatment with only corn oil, as well as mice with no treatment. Tendons were evaluated by measuring the quasi-static and viscoelastic mechanics, collagen fiber realignment, cellularity, and nuclear morphology.</p><p><strong>Results: </strong>Mechanical testing of the tendons post-injury revealed no changes to viscoelastic mechanics, quasi-static mechanics, or collagen realignment during loading after tamoxifen treatment with the dosage regimen utilized (three daily injections of 4.5 mg/40 g body weight). Additionally, histological analysis revealed no changes to cellularity or cell nuclear shape.</p><p><strong>Conclusion: </strong>Overall, this study revealed that tamoxifen treatment at the time of tendon injury did not result in changes to tendon mechanics or the histological parameters at 3 weeks post-injury.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9383640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of aging on tendon homeostasis, tendinopathy development, and impaired healing.","authors":"Antonion Korcari, Samantha J Przybelski, Anne Gingery, Alayna E Loiselle","doi":"10.1080/03008207.2022.2102004","DOIUrl":"10.1080/03008207.2022.2102004","url":null,"abstract":"<p><p>Aging is a complex and progressive process where the tissues of the body demonstrate a decreased ability to maintain homeostasis. During aging, there are substantial cellular and molecular changes, with a subsequent increase in susceptibility to pathological degeneration of normal tissue function. In tendon, aging results in well characterized alterations in extracellular matrix (ECM) structure and composition. In addition, the cellular environment of aged tendons is altered, including a marked decrease in cell density and metabolic activity, as well as an increase in cellular senescence. Collectively, these degenerative changes make aging a key risk factor for the development of tendinopathies and can increase the frequency of tendon injuries. However, inconsistencies in the extent of age-related degenerative impairments in tendons have been reported, likely due to differences in how \"old\" and \"young\" age-groups have been defined, differences between anatomically distinct tendons, and differences between animal models that have been utilized to study the impact of aging on tendon homeostasis. In this review, we address these issues by summarizing data by well-defined age categories (young adults, middle-aged, and aged) and from anatomically distinct tendon types. We then summarize in detail how aging affects tendon mechanics, structure, composition, and the cellular environment based on current data and underscore what is currently not known. Finally, we discuss gaps in the current understanding of tendon aging and propose key avenues for future research that can shed light on the specific mechanisms of tendon pathogenesis due to aging.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report.","authors":"Bahareh Sadri,&nbsp;Atena Tamimi,&nbsp;Shirin Nouraein,&nbsp;Abolfazl Bagheri Fard,&nbsp;Javad Mohammadi,&nbsp;Mehdi Mohammadpour,&nbsp;Mohammad Hassanzadeh,&nbsp;Amir Bajouri,&nbsp;Hoda Madani,&nbsp;Maryam Barekat,&nbsp;Shahedeh Karimi Torshizi,&nbsp;Mahrooz Malek,&nbsp;Maede Ghorbani Liastani,&nbsp;Alireza Beheshti Maal,&nbsp;Maryam Niknejadi,&nbsp;Massoud Vosough","doi":"10.1080/03008207.2022.2074841","DOIUrl":"https://doi.org/10.1080/03008207.2022.2074841","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stromal cells (MSCs) injection has been proposed as an innovative treatment for knee osteoarthritis (KOA). Since, allogeneic MSCs can be available as off-the-shelf products, they are preferable in regenerative medicine. Among different sources for MSCs, adipose-derived MSCs (AD-MSCs) appear to be more available.</p><p><strong>Methods: </strong>Three patients with KOA were enrolled in this study. A total number of 100 × 10⁶ AD-MSCs was injected intra-articularly, per affected knee. They were followed up for 6 months by the assessment of clinical outcomes, magnetic resonance imaging (MRI), and serum inflammatory biomarkers.</p><p><strong>Results: </strong>The primary outcome of this study was safety and feasibility of allogeneic AD-MSCs injection during the 6 months follow-up. Fortunately, no serious adverse events (SAEs) were reported. Assessment of secondary outcomes of visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and knee osteoarthritis outcome score (KOOS) indicated improvement in all patients. Comparison between baseline and endpoint findings of MRI demonstrated a slight improvement in two patients. In addition, decrease in serum cartilage oligomeric matrix protein (COMP) and hyaluronic acid (HA) indicated the possibility of reduced cartilage degeneration. Moreover, quantification of serum interleukin-10 (IL-10) and interleukin-6 (IL-6) levels indicated that the host immune system immunomodulated after infusion of AD-MSCs.</p><p><strong>Conclusion: </strong>Intra-articular injection of AD-MSCs is safe and could be effective in cartilage regeneration in KOA. Preliminary assessment after six-month follow-up suggests the potential efficacy of this intervention which would need to be confirmed in randomized controlled trials on a larger population.</p><p><strong>Trial registration: </strong>This study was registered in the Iranian registry of clinical trials (https://en.irct.ir/trial/46) in 24 April 2018 with identifier IRCT20080728001031N23.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10469267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K/Akt pathway delaying intervertebral disc degeneration.","authors":"Hai-Wei Chen,&nbsp;Ming-Qiang Liu,&nbsp;Guang-Zhi Zhang,&nbsp;Cang-Yu Zhang,&nbsp;Zhao-Heng Wang,&nbsp;Ai-Xin Lin,&nbsp;Ji-He Kang,&nbsp;Wen-Zhao Liu,&nbsp;Xu-Dong Guo,&nbsp;Yi-Dian Wang,&nbsp;Xue-Wen Kang","doi":"10.1080/03008207.2022.2063121","DOIUrl":"https://doi.org/10.1080/03008207.2022.2063121","url":null,"abstract":"<p><strong>Background: </strong>Low back pain is a common symptom of intervertebral disc degeneration (IDD), which seriously affects the quality of life of patients. The abnormal apoptosis and senescence of nucleus pulposus (NP) cells play important roles in the pathogenesis of IDD. Proanthocyanidins (PACs) are polyphenolic compounds with anti-apoptosis and anti-aging effects. However, their functions in NP cells are not yet clear. Therefore, this study was performed to explore the effects of PACs on NP cell apoptosis and aging and the underlying mechanisms of action.</p><p><strong>Methods: </strong>Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined TUNEL assays. Levels of apoptosis-associated molecules (Bcl-2, Bax, C-caspase-3 and Caspase-9) were evaluated via western blot. The senescence was observed through SA-β-gal staining and western blotting analysis was performed to observe the expression of senescence-related molecules (p-P53, P53, P21 and P16).</p><p><strong>Results: </strong>Pretreatment with PACs exhibited protective effects against IL-1β-induced NP cell apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. PACs could also alleviate the increase of p-p53, P21, and P16 in IL-1β-treated NP cells. SA-β-gal staining showed that IL-1β-induced senescence of NP cells was prevented by PACs pertreatment. In addition, PACs activated PI3K/Akt pathway in IL-1β-stimulated NP cells. However, these protected effects were inhibited after LY294002 treatment.</p><p><strong>Conclusion: </strong>The results of the present study showed that PACs inhibit IL-1β-induced apoptosis and aging of NP cells by activating the PI3K/Akt pathway, and suggested that PACs have therapeutic potential for IDD.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10219820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclic mechanical stretch regulates the AMPK/Egr1 pathway in tenocytes via Ca2+-mediated mechanosensing.","authors":"Yu-Ting Huang,&nbsp;Yu-Fu Wu,&nbsp;Hsing-Kuo Wang,&nbsp;Chung-Chen Jane Yao,&nbsp;Yi-Heng Chiu,&nbsp;Jui-Sheng Sun,&nbsp;Yuan-Hung Chao","doi":"10.1080/03008207.2022.2044321","DOIUrl":"https://doi.org/10.1080/03008207.2022.2044321","url":null,"abstract":"<p><strong>Purpose: </strong>Mechanical stimuli are essential for the maintenance of tendon tissue homeostasis. The study aims to elucidate the mechanobiological mechanisms underlying the maintenance of tenocyte homeostasis by cyclic mechanical stretch under high-glucose (HG) condition.</p><p><strong>Materials and methods: </strong>Primary tenocytes were isolated from rat Achilles tendon and 2D-cultured under HG condition. The <i>in vitro</i> effects of a single bout, 2-h cyclic biaxial stretch session (1 Hz, 8%) on primary rat tenocytes were explored through Flexcell system. Cell viability, tenogenic gene expression, intracellular calcium concentration, focal adhesion kinase (FAK) expression, and signaling pathway activation were analyzed in tenocytes with or without mechanical stretch.</p><p><strong>Results: </strong>Mechanical stretch increased tenocyte proliferation and upregulated early growth response protein 1 (Egr1) expression. An increase in intracellular calcium was observed after 30 min of stretching. Mechanical stretch phosphorylated FAK, calmodulin-dependent protein kinase kinase 2 (CaMKK2), and 5' adenosine monophosphate-activated protein kinase (AMPK) in a time-dependent manner, and these effects were abrogated after blocking intracellular calcium. Inhibition of FAK, CaMKK2, and AMPK downregulated the expression of Egr1. In addition, mechanical stretch reinforced cytoskeletal organization via calcium (Ca2+)/FAK signaling.</p><p><strong>Conclusions: </strong>Our study demonstrated that mechanical stretch-induced calcium influx activated CaMKK2/AMPK signaling and FAK-cytoskeleton reorganization, thereby promoting the expression of Egr1, which may help maintain tendon cell characteristics and homeostasis in the context of diabetic tendinopathy.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10757517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inhibitory effect of tocilizumab on systemic bone loss and tendon inflammation in a juvenile Collagen-Induced arthritis rat model.","authors":"Frideriki Poutoglidou,&nbsp;Chryssa Pourzitaki,&nbsp;Maria Eleni Manthou,&nbsp;Efthimios Samoladas,&nbsp;Athanasios Saitis,&nbsp;Foteini Malliou,&nbsp;Dimitrios Kouvelas","doi":"10.1080/03008207.2022.2042275","DOIUrl":"https://doi.org/10.1080/03008207.2022.2042275","url":null,"abstract":"<p><strong>Purpose of the study: </strong>Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA.</p><p><strong>Materials and methods: </strong>The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis.</p><p><strong>Results: </strong>Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue.</p><p><strong>Conclusions: </strong>The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39807459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Nrf2 and HO-1 in intervertebral disc degeneration.","authors":"Cang-Yu Zhang,&nbsp;Xu-Chang Hu,&nbsp;Guang-Zhi Zhang,&nbsp;Ming-Qiang Liu,&nbsp;Hai-Wei Chen,&nbsp;Xue-Wen Kang","doi":"10.1080/03008207.2022.2089565","DOIUrl":"https://doi.org/10.1080/03008207.2022.2089565","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is a common age-related disease with clinical manifestations of lumbar and leg pain and limited mobility. The pathogenesis of IDD is mainly mediated by the death of intervertebral disc (IVD) cells and the imbalance of extracellular matrix (ECM) synthesis and degradation. Oxidative stress and inflammatory reactions are the important factors causing this pathological change. Therefore, the regulation of reactive oxygen species and production of inflammatory factors may be an effective strategy to delay the progression of IDD. In recent years, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream regulated protein heme oxygenase-1 (HO-1) have received special attention due to their antioxidant, anti-inflammatory and anti-apoptotic protective effects. Recent studies have elucidated the important role of these two proteins in the treatment of IDD disease. However, Nrf2 and HO-1 have not been systematically reported in IDD-related diseases. Therefore, this review describes the biological characteristics of Nrf2 and HO-1, the relationship between Nrf2- and HO-1-regulated oxidative stress and the inflammatory response and IDD, and the progress in research on some extracts targeting Nrf2 and HO-1 to improve IDD. Understanding the role and mechanism of Nrf2 and HO-1 in IDD may provide novel ideas for the clinical treatment and development of Nrf2- and HO-1-targeted drugs.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40255360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of cells on spatial quantification of proteoglycans in articular cartilage of small animals.","authors":"Kalle Karjalainen, Petri Tanska, Scott C Sibole, Santtu Mikkonen, Walter Herzog, Rami K Korhonen, Eng Kuan Moo","doi":"10.1080/03008207.2022.2048827","DOIUrl":"10.1080/03008207.2022.2048827","url":null,"abstract":"<p><strong>Objective: </strong>Histochemical characterization of proteoglycan content in articular cartilage is important for the understanding of osteoarthritis pathogenesis. However, cartilage cells may interfere with the measurement of matrix proteoglycan content in small animal models (e.g. mice and rats) due to the high cell volume fraction (38%) in mice compared to human tissue (~1%). We investigated whether excluding the cells from image analysis affects the histochemically measured proteoglycan content of rat knee joint cartilage and assessed the effectiveness of a deep learning algorithm-based tool named U-Net in cell segmentation.</p><p><strong>Design: </strong>Histological sections were stained with Safranin-O, after which optical densities were measured using digital densitometry to estimate proteoglycan content. U-Net was trained with 600 annotated Safranin-O cartilage images for exclusion of cells from the cartilage extracellular matrix. Optical densities of the ECM with and without cells were compared as a function of normalized tissue depth.</p><p><strong>Results: </strong>U-Net cell segmentation was accurate, with the measured cell area fraction following largely that of ground-truth images (average difference: 4.3%). Cell area fraction varied as a function of tissue depth and took up 8-21% of the tissue area. The exclusion of cells from the analysis led to an increase in the analyzed depth-dependent optical density of cartilage by approximately 0.6-1.8% (<i>p</i> < 0.01).</p><p><strong>Conclusions: </strong>Although the effect of cells on the analyzed proteoglycan content is small, it should be considered for improved sensitivity, especially at the onset of the disease during which cells may proliferate in small animals.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10774449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The protective role of glucocerebrosidase/ceramide in rheumatoid arthritis.","authors":"Mingfeng Yang,&nbsp;Juanfang Gu,&nbsp;Fangyan Xu,&nbsp;Yiwen Wang,&nbsp;Hongzhi Wang,&nbsp;Bin Zhang","doi":"10.1080/03008207.2022.2055552","DOIUrl":"https://doi.org/10.1080/03008207.2022.2055552","url":null,"abstract":"<p><strong>Objective: </strong>To clarify the role of glucocerebrosidase (GBA) and Ceramide (Cer) in rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>GBA-expressing lentivirus were constructed and injected into collagen-induced arthritis (CIA) mice, and compared with CIA mice injected with empty vector. The severity of arthritis and inflammatory mediators were evaluated. Fibroblast-like synoviocytes (FLS) from RA patients were transfected with GBA-expressing lentivirus, or pretreated with C6-Cer. The migration and invasion of FLS, the production of inflammatory cytokines, and the relevant signaling pathways were assessed.</p><p><strong>Results: </strong>In CIA mice, GBA markedly improved arthritis compared to that in the CIA mice, with increased content of proteoglycan and integral cartilage surfaces and tidemarks. The circulating inflammatory mediators, including interleukin (IL)-1β, IL-6, IL-18, and matrix metalloproteinase (MMP)-1, were significantly reduced in CIA mice with GBA overexpression compared to those in CIA mice. GBA and C6-Cer treatment inhibited migration and invasion of FLS, and suppressed production of inflammatory cytokines and activation of the MAPK pathways.</p><p><strong>Conclusion: </strong>GBA/Cer exhibited a protective role in CIA mice and RA FLS. These results highlight the potential of targeting GBA/Cer as a therapeutic strategy in RA and warrant further investigation.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40310686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the symptoms of post-traumatic osteoarthritis by α2-macroglobulin-rich serum.","authors":"Xiaohu Wang,&nbsp;Lu Li,&nbsp;Xiaochun Wei,&nbsp;Pengcui Li,&nbsp;Yu Zhao,&nbsp;Ruipeng Zhao,&nbsp;Zhiqing Duan","doi":"10.1080/03008207.2022.2051499","DOIUrl":"https://doi.org/10.1080/03008207.2022.2051499","url":null,"abstract":"<p><strong>Purpose: </strong>Altered joint loading by trauma induces joint degeneration, eventually leading to the generation of post-traumatic osteoarthritis (PTOA). Recent studies have shown that α2-macroglobulin (A2M) inhibits PTOA, induced by anterior cruciate ligament transection (ACLT), pathogenesis by regulating proinflammatory cytokines and matrix metalloproteinases. However, the application of A2M is limited due to high prices. Therefore, the aim of this study is to explore the novel preparation of A2M.</p><p><strong>Materials and methods: </strong>The early change of A2M in synovial fluid and serum was measured by ELISA. Ultra-filtered centrifugation was performed to prepare α2-macroglobulin-rich serum (A2MRS). The bioactivity of A2M in A2MRS was detected by improved Ellis and Gollas-Galvan method. The effects of A2MRS on PTOA were observed using immunohistochemistry, safranine O staining, micro X-ray, fluorescence molecular tomography etc.</p><p><strong>Results: </strong>The concentration of A2M in PTOA group was significantly higher than that in Sham group in synovial fluid on the third day after ACLT in rat PTOA model. On the contrary, a significant downregulation of A2M levels in PTOA group was observed compared to the Sham group in serum at the seventh day after ACLT. Secondly, A2MRS was prepared successfully, and the concentration and bioactivity of A2M in A2MRS was significantly higher than that in serum. Lastly, A2MRS not only reduced notably the production of secondary cartilage ossification, type 10 collagen and matrix metalloproteinase 13, but also increased profoundly the generation of type 2 collagen, aggrecan, and chondrocytes' number.</p><p><strong>Conclusion: </strong>Our results indicate that A2MRS has protective effects on PTOA.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40310804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}