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简介：AbstractMany factors can cause inner ear injury, such as noise exposure, chemicals, viral infection, and radiation. The main pathological manifestations of inner ear injury are local hypoxia-ischemia, micro-trauma, and an increased level of reactive oxygen species and inflammatory mediators. The contribution of the inflammatory response to the mediation of cochlear and vestibular pathologies has received increasing attention in recent years. Aseptic inflammation can devastate audition and balance, which can lead to many typical clinical inner ear diseases. In this review, we will discuss the most pertinent and recent research on inflammatory mechanisms in inner ear injury. We will also discuss the pathophysiology of some common and significant ear diseases, such as sudden sensorineural hearing loss, age-related hearing loss, noise-induced hearing loss, and Meniere’s disease.

简介：AbstractWith the deepening of research, proteomics has developed into a science covering the study of all the structural and functional characteristics of proteins and the dynamic change rules. The essence of various biological activities is revealed from the perspectives of the biological structure, functional activity and corresponding regulatory mechanism of proteins by proteomics. Among them, phospholipid-binding protein is one of the hotspots of proteomics, especially annexin A1, which is widely present in various tissues and cells of the body. It has the capability of binding to phospholipid membranes reversibly in a calcium ion dependent manner. In order to provide possible research ideas for researchers, who are interested in this protein, the biological effects of annexin A1, such as inflammatory regulation, cell signal transduction, cell proliferation, differentiation and apoptosis are described in this paper.

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简介：AbstractCerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.

简介：AbstractType 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.

简介：AbstractAspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyposis, adult-onset asthma and non-IgE mediated reactions to aspirin and other cyclooxygenase-1 (COX-1) inhibitors. Patients with AERD are dependent on COX-1 activity to maintain production of prostaglandin (PG) species, such as PGE2, which maintain physiologic levels of inflammation and limit the production of pro-inflammatory cysteinyl leukotrienes. The endogenous cannabinoid system is a family of immunomodulatory lipids and their innate g-protein coupled receptors that are closely related to arachidonic acid and may modulate inflammation via several pathways, including the direct production of metabolically active prostaglandin glycerol-esters. A recent pilot study has identified the significant up-regulation of the peripherally expressed, type-2 cannabinoid receptor (CB2) in AERD nasal polyps versus control tissues from patients with either allergic fungal rhinosinusitis or no history of chronic sinonasal inflammation. These early findings suggest the involvement of increased endogenous cannabinoid activity in prostaglandin deficient states such as AERD. Future study is needed to explore the significance of these findings, with specific investigation of the impact of CB2 activation on markers of airway inflammation, as well as the potential to measure CB2 expression as a screening biomarker for the evaluation of unrecognized disease.

简介：AbstractImportance:The impact of long-term burden of excessive body weight, beginning in childhood, on inflammatory status in adulthood has been poorly described.Objective:To characterize the longitudinal body mass index (BMI) trajectory from childhood and examine its relationship with inflammatory status in adulthood.Methods:We included 1285 adults who had 4-15 repeat measurements of BMI from childhood to adulthood. The area under the curve (AUC) of growth curves was calculated to characterize long-term burden (total AUC) and trends (incremental AUC) of BMI.Results:After adjusting for covariates, higher values of BMI in terms of childhood and adulthood, as well as total and incremental AUC, were strongly associated with elevated levels of adult C-reactive protein (CRP) in the four race-sex groups. There were significant differences in linear and nonlinear curve parameters between the normal and high CRP groups for all race-sex groups (P < 0.01). Compared with participants who had consistently low BMI in both childhood and adulthood, participants with high BMI in adulthood had higher CRP levels (P < 0.001), irrespective of their childhood BMI status; participants with high BMI in childhood but low BMI in adulthood had similar adult CRP levels.Interpretation:The impact of excessive body weight on inflammation is cumulative and exacerbated over time. The influence of childhood overweight/obesity on inflammatory status in adulthood can be alleviated by reducing adiposity in adulthood.

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简介：AbstractBackground:Psoriasis is a common chronic inflammatory skin disease with 2% to 3% prevalence worldwide and a heavy social-psychological burden for patients and their families. As the exact pathogenesis of psoriasis is still unknown, the current treatment is far from satisfactory. Thus, there is an urgent need to find a more effective therapy for this disease. Keratin 17 (K17), a type I intermediate filament, is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis. Therefore, we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis. This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA (siRNA) on mice with imiquimod (IMQ)-induced psoriasis-like dermatitis.Methods:Eight-week-old female BALB/c mice were administered a 5% IMQ cream on both ears to produce psoriatic dermatitis. On day 3, K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days. The right ears of the mice were treated in parallel with negative control (NC) siRNA. Inflammation was evaluated by gross ear thickness, histopathology, the infiltration of inflammatory cells (CD3+ T cells and neutrophils) using immunofluorescence, and the expression of cytokine production using real-time quantitative polymerase chain reaction. The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance.Results:The severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears, as evidenced by the alleviated ear inflammation phenotype, including decreased ear thickness, infiltration of inflammatory cells (CD3+ T cells and neutrophils), and inflammatory cytokine/chemokine expression levels (interleukin 17 [IL-17], IL-22, IL-23, C-X-C motif chemokine ligand 1, and C-C motif chemokine ligand 20) (P < 0.05 vs. the Blank or NC siRNA groups). Compared to the NC siRNA treatment, the K17 siRNA treatment resulted in increased K1 and K10 expression, which are characteristic of keratinocyte differentiation (vs. NC siRNA, K17 siRNA1 group: K1, t= 4.782, P= 0.0050; K10, t= 3.365, P= 0.0120; K17 siRNA2 group: K1, t= 4.104, P= 0.0093; K10, t= 4.168, P= 0.0042; siRNA Mix group: K1, t= 3.065, P = 0.0221; K10, t = 10.83, P < 0.0001), and decreased K16 expression, which is characteristic of keratinocyte proliferation (vs. NC siRNA, K17 siRNA1 group: t= 4.156, P= 0.0043; K17 siRNA2 group: t= 2.834, P= 0.0253; siRNA Mix group: t= 2.734, P = 0.0250).Conclusions:Inhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis. Thus, gene therapy targeting K17 may be a potential treatment approach for psoriasis.

简介：AbstractBackground:Cardiac remodeling after acute myocardial infarction (AMI) is an important process. The present study aimed to assess the protective effects of astaxanthin (ASX) on cardiac remodeling after AMI.Methods:The study was conducted between April and September 2018. To create a rat AMI model, rats were anesthetized, and the left anterior descending coronary artery was ligated. The rats in the ASX group received 10 mg·kg-1·day-1 ASX by gavage for 28 days. On the 1st day after AMI, but before ASX administration, six rats from each group were sacrificed to evaluate changes in the heart function and peripheral blood (PB) levels of inflammatory factors. On the 7th day after AMI, eight rats from each group were sacrificed to evaluate the PB levels of inflammatory factors and the M2 macrophage count using both immunofluorescence (IF) and flow cytometry (FC). The remaining rats were observed for 28 days. Cardiac function was examined using echocardiography. The inflammatory factors, namely, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, were assessed using enzyme-linked immunosorbent assay. The heart weight/body weight (BW), and lung weight (LW)/BW ratios were calculated, and myocardial fibrosis in the form of collagen volume fraction was measured using Masson trichrome staining. Hematoxylin and eosin (H&E) staining was used to determine the myocardial infarct size (MIS), and TdT-mediated dUTP nick-end labeling staining was used to analyze the myocardial apoptosis index. The levels of apoptosis-related protein, type I/III collagen, transforming growth factor β1 (TGF-β1), metalloproteinase 9 (MMP9), and caspase 3 were assessed by Western blotting. Unpaired t-test, one-way analysis of variance, and non-parametric Mann-Whitney test were used to analyze the data.Results:On day 1, cardiac function was worse in the ASX group than in the sham group (left ventricular end-systolic diameter [LVIDs]: 0.72 ± 0.08 vs. 0.22 ± 0.06 cm, t= -11.38; left ventricular end-diastolic diameter [LVIDd]: 0.89 ± 0.09 vs. 0.48 ± 0.05 cm, t= -9.42; end-systolic volume [ESV]: 0.80 [0.62, 0.94] vs. 0.04 [0.03, 0.05] mL, Z = -2.89; end-diastolic volume [EDV]: 1.39 [1.03, 1.49] vs. 0.28 [0.22, 0.32] mL, Z = -2.88; ejection fraction [EF]: 0.40 ± 0.04 vs. 0.86 ± 0.05, t= 10.00; left ventricular fractional shortening [FS] rate: 0.19 [0.18, 0.20] %FS vs. 0.51 [0.44, 0.58] %FS, Z = -2.88, all P < 0.01; n = 6). The levels of inflammatory factors significantly increased (TNF-α: 197.60 [133.89, 237.94] vs. 50.48 [47.21 57.10] pg/mL, Z= -2.88; IL-1β: 175.23 [160.74, 215.09] vs. 17.78 [16.83, 19.56] pg/mL, Z = -2.88; IL-10: 67.64 [58.90, 71.46] vs. 12.33 [11.64, 13.98] pg/mL, Z = -2.88, all P < 0.01; n = 6). On day 7, the levels of TNF-α and IL-1β were markedly lower in the ASX group than in the AMI group (TNF-α: 71.70 [68.60, 76.00] vs. 118.07 [106.92, 169.08] pg/mL, F = 42.64; IL-1β: 59.90 [50.83, 73.78] vs. 151.60 [108.4, 198.36] pg/mL, F = 44.35, all P < 0.01, n = 8). Conversely, IL-10 levels significantly increased (141.84 [118.98, 158.36] vs. 52.96 [42.68, 74.52] pg/mL, F= 126.67, P < 0.01, n = 8). The M2 macrophage count significantly increased (2891.42 ± 211.29 vs. 1583.38 ± 162.22, F= 274.35, P < 0.01 by immunofluorescence test; 0.96 ± 0.18 vs. 0.36 ± 0.05, F= 46.24, P < 0.05 by flowcytometry test). On day 28, cardiac function was better in the ASX group than in the AMI group (LVIDs: 0.50 [0.41, 0.56] vs. 0.64 [0.56, 0.74] cm, Z = -3.60; LVIDd: 0.70 [0.60, 0.76] vs. 0.80 [0.74 0.88] cm, Z = -2.96; ESV: 0.24 [0.18, 0.45] vs. 0.58 [0.44, 0.89] mL, Z = -3.62; EDV: 0.76 [0.44, 1.04] vs. 1.25 [0.82, 1.46] mL, Z = -2.54; EF: 0.60 ± 0.08 vs. 0.50 ± 0.12, F= 160.48; % FS: 0.29 [0.24, 0.31] vs. 0.20 [0.17, 0.21], Z = -4.43, all P < 0.01; n = 16). The MIS and LW/BW ratio were markedly lower in the ASX group than in the AMI group (myocardial infarct size: 32.50 ± 1.37 vs. 50.90 ± 1.73, t = 23.63, P < 0.01, n = 8; LW/BW: 1.81 ± 0.15 vs. 2.17 ± 0.37, t= 3.66, P = 0.01, n = 16). The CVF was significantly lower in the ASX group than in the AMI group: 12.88 ± 2.53 vs. 28.92 ± 3.31, t = 10.89, P < 0.01, n = 8. The expression of caspase 3, TGF-β1, MMP9, and type I/III collagen was lower in the ASX group than in the AMI group (caspase 3: 0.38 ± 0.06 vs. 0.66 ± 0.04, t= 8.28; TGF-β1: 0.37 ± 0.04 vs. 0.62 ± 0.07, t = 6.39; MMP9: 0.20 ± 0.06 vs. 0.40 ± 0.06, t = 4.62; type I collagen: 0.42 ± 0.09 vs. 0.74 ± 0.07, t = 5.73; type III collagen: 0.13 ± 0.02 vs. 0.74 ± 0.07, t = 4.32, all P < 0.01; n = 4).Conclusions:ASX treatment after AMI may promote M2 macrophages and effectively attenuate cardiac remodeling by inhibiting inflammation and reducing myocardial fibrosis.

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简介：AbstractBackground:Previous evidence suggests inflammation may be a double-edged sword with cancer-promoting and cancer suppressing function. In this study, we explore the impact of local and systemic inflammation on cancer growth.Methods:Female BALB/C mice were subcutaneously implanted with foreign body (plastic plates) to build up a local inflammation and intraperitoneally injected with PolyIC or lipopolysaccharides (LPS) to build up a systemic inflammation, followed by subcutaneous injection of 5 × 105 colon cancer cells. Immunohistochemistry and enzyme linked immunosorbent assay were utilized to detect the Ki67 and interleukin (IL) 6, IL-1β, and monocyte chemoattractant protein-1 expression in the tumor tissues and serum, respectively. The distributions of immune cells and expression of toll-like receptors (TLRs) were evaluated by flow cytometry (FCM) and quantitative real time-polymerase chain reaction.Results:The results showed that local inflammation induced by foreign body implantation suppressed tumor growth with decreased tumor weight (P = 0.001), volume (P = 0.004) and Ki67 index (P < 0.001). Compared with the control group, myeloid-derived suppressive cells sharply decreased (P = 0.040), while CD4+ T cells slightly increased in the tumor tissues of the group of foreign body-induced local inflammation (P = 0.035). Moreover, the number of M1 macrophages (P = 0.040) and expression of TLRs, especially TLR3 (P < 0.001) and TLR4 (P < 0.001), were significantly up-regulated in the foreign body group. Contrarily, tumor growth was significantly promoted in LPS or PolyIC-induced systemic inflammation (P = 0.009 and 0.006). FCM results showed M1 type macrophages (P = 0.017 and 0.006) and CD8+ T cells (P = 0.031 and 0.023) were decreased, while M2 type macrophages (P = 0.002 and 0.007) were significantly increased in tumor microenvironment of LPS or PolyIC-induced systemic inflammation group. In addition, the decreased expression of TLRs was detected in LPS or PolyIC group.Conclusions:The foreign body-induced local inflammation inhibited tumor growth, while LPS or PolyIC-induced systemic inflammation promoted tumor growth. The results suggested that the different outcomes of tumor growth might be attributed to the infiltration of anti-tumor or pro-tumor immune cells, especially M1 or M2 type macrophages into tumor microenvironment.

简介：AbstractBackground:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism.Methods:SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.Results:Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2 ± 30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3 ± 46.8 vs. 421.7 ± 48.3 pg/ml; amylase: 2102.3 ± 165.3 vs. 3186.4 ± 245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 ± 50.3 vs. 332.4 ± 25.1 Hz; discharge amplitude: 33.4 ± 5.3 vs. 20.5 ± 2.9 μV).Conclusions:Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus-and α7nAChR-dependent mechanisms.

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简介：AbstractBackground:Pulmonary arterial hypertension (PH) is a progressive disease with limited therapeutic options, ultimately leading to right heart failure and death. Recent findings indicate the role of the Warburg effect (aerobic glycolysis) in the development of PH. However, the effect of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the pathogenesis of PH has not been well investigated. This study aimed to determine whether 3-BrPA inhibits PH and its possible mechanism.Methods:PH was induced in adult Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT). 3-BrPA, or phosphate-buffered saline (PBS) was administered via intraperitoneal injection every other day from the first day of MCT-injection to 4 weeks of follow-up, and indices such as right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary arteriolar remodeling indicated by percent media thickness (% MT), lactate levels and glucose consumption, were evaluated. Pulmonary arteriolar remodeling and right ventricular hypertrophy were observed in hematoxylin-eosin-stained lung sections. Western blotting, immunohistochemistry, and/or immunofluorescence analyses were used to measure the expression of relevant proteins. A cytochrome C release apoptosis assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining were used to measure cell apoptosis.Results:MCT-induced PH showed a significant increase in glucose consumption (0 vs. 4 weeks: 0.87 ± 0.23 vs. 2.94 ± 0.47, P = 0.0042) and lactate production (0 vs. 4 weeks: 4.19 ± 0.34 vs. 8.06 ± 0.67, P = 0.0004). Treatment with 3-BrPA resulted in a concomitant reduction in glucose consumption (1.10 ± 0.35 vs. 3.25 ± 0.47, P = 0.0063), lactate production (5.09 ± 0.55 vs. 8.06 ± 0.67, P= 0.0065), MCT-induced increase in RVSP (39.70 ± 2.94 vs. 58.85 ± 2.32, P= 0.0004), pulmonary vascular remodeling (% MT, 43.45% ± 1.41% vs. 63.66% ± 1.78%, P < 0.0001), and right ventricular hypertrophy (RVHI, 38.57% ± 2.69% vs. 62.61% ± 1.57%, P < 0.0001) when compared with those of the PBS-treated group. 3-BrPA, a hexokinase 2 inhibitor, exerted its beneficial effect on PH by decreasing aerobic glycolysis and was also associated with inhibiting the expression of glucose transporter protein-1, inducing apoptosis, and suppressing inflammation.Conclusions:3-BrPA might have a potential beneficial effect on the PH treatment.

简介：AbstractBackground:The casein kinase 2-interacting protein-1 (CKIP-1) is important in the development of osteoblasts and cardiomyocytes. However, the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells (MSCs) remain unclear. This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation.Methods:Bone marrow MSCs of CKIP-1 wild type (WT) and knockout (KO) mice were cultivated in vitro. Cell phenotype was analyzed by flow cytometry, colony formation was detected to study the proliferative ability. Osteogenic and adipogenic induction were performed. The osteogenic ability was explored by alizarin red staining, alkaline phosphatase (ALP) staining and ALP activity detection. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the mRNA expression levels of osteoblast marker genes. The adipogenic ability was detected by oil red O staining. Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume (BV/TV), bone surface area fraction/trabecular BV, trabecular number (Tb.N), and trabecular spacing (Tb.sp). Interleukin (IL)-1β was injected on WT mice of 2 months old and 18 months old, respectively. Difference in CKIP-1 expression was detected by RT-PCR and western blot. The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot.Results:ALP assays, alizarin red staining, and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis. Micro-computed tomography detection showed that among 18-month-old mice, CKIP-1 KO mice presented significantly higher bone mass compared with WT mice (P = 0.02). No significant difference was observed in 2-month-old mice. In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice (4.3-fold increase at the mRNA level, P = 0.04). Finally, the expression levels of CKIP-1 in bone marrow (3.2-fold increase at the mRNA level, P = 0.03) and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1β.Conclusions:CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects. Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.

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