Soluble CD14 and fracture risk

Bethel, Monique; Bůžková, Petra; Fink, Howard A; Robbins, John A.; Cauley, Jane A.; Lee, J.; Barzilay, Joshua I.; Jalal, Diana; Carbone, Laura D

doi:10.1007/s00198-015-3439-9

Cited by 7 publications

(3 citation statements)

References 56 publications

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“…In women without HIV, we observed a more linear increase in sCD14 over time, suggestive of chronological aging, and consistent with positive associations of age and sCD14 in other populations without HIV. 38 We speculate that in women with HIV, where HIV infection is driving higher sCD14 levels, the effect of aging on sCD14 is diminished, whereas the effect of the menopausal transition on sCD14 is more apparent; in women without HIV, the gradual increase in sCD14 with aging may diminish the effect of the menopausal transition on sCD14. Consistently, a lack of association between age and sCD14 in people with HIV on ART has been previously observed.…”

Section: Discussionmentioning

confidence: 86%

Menopause and estrogen associations with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV

Peters,

Hanna,

Xue

et al. 2024

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objectives: Estrogens may protect the gut barrier and reduce microbial translocation and immune activation, which are prevalent in HIV infection. We investigated relationships of the menopausal transition and estrogens with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV. Design: Longitudinal and cross-sectional studies nested in the Women's Interagency HIV Study. Methods: Intestinal fatty acid binding protein, lipopolysaccharide binding protein, and soluble CD14 (sCD14) levels were measured in serum from 77 women (43 with HIV) before, during, and after the menopausal transition (∼6 measures per woman over ∼13 years). A separate cross-sectional analysis was conducted among 72 postmenopausal women with HIV with these biomarkers and serum estrogens. Results: Women in the longitudinal analysis were a median age of 43 years at baseline. In piecewise, linear, mixed-effects models with cutpoints 2 years before and after the final menstrual period to delineate the menopausal transition, sCD14 levels increased over time during the menopausal transition (Beta [95% CI]: 38 [12 to 64] ng/mL/yr, P = 0.004), followed by a decrease posttransition (−46 [−75 to −18], P = 0.001), with the piecewise model providing a better fit than a linear model (P = 0.0006). In stratified analyses, these results were only apparent in women with HIV. In cross-sectional analyses, among women with HIV, free estradiol inversely correlated with sCD14 levels (r = −0.26, P = 0.03). Lipopolysaccharide binding protein and intestinal fatty acid binding protein levels did not appear related to the menopausal transition and estrogen levels. Conclusions: Women with HIV may experience heightened innate immune activation during menopause, possibly related to the depletion of estrogens.

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Section: Discussionmentioning

confidence: 86%

Menopause and estrogen associations with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV

Peters,

Hanna,

Xue

et al. 2024

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…CD163 and CD14 are positively associated with the severity of H. pylori infection and CD163 was also positively correlated with fracture 50 , 51 . Soluble CD14(sCD14), a proinflammatory cytokine, is primarily derived from macrophages/monocytes that can differentiate into osteoclasts, and sCD14 is an inflammatory marker associated with osteoclasts 52 . Gastritis and gastric tumorigenesis are associated with upregulation of CCR1 53 .…”

Section: Discussionmentioning

confidence: 99%

Clinical features and shared mechanisms of chronic gastritis and osteoporosis

Han

Zhang

et al. 2023

Sci Rep

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Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the GEO2R tool and the Venny platform. Protein–protein interaction information was obtained by inputting the intersection targets into the STRING database. The PPI network was constructed by Cytoscape v3.6.0 software again, and the key genes were screened out according to the degree value. Gene function enrichment of DEGs was performed by Webgestalt online tool. One hundred and thirty CG patients were finally included in this study. Univariate correlation analysis showed that age, gender, BMI and coffee were the potential influencing factors for the comorbidity (P < 0.05). Multivariate Logistic regression model found that smoking history, serum PTH and serum β-CTX were positively correlated with OP in CG patients, while serum P1NP and eating fruit had an negative relationship with OP in CG patients. In studies of the shared mechanisms, a total of 76 intersection genes were identified between CG and OP, including CD163, CD14, CCR1, CYBB, CXCL10, SIGLEC1, LILRB2, IGSF6, MS4A6A and CCL8 as the core genes. The biological processes closely related to the occurrence and development of CG and OP mainly involved Ferroptosis, Toll-like receptor signaling pathway, Legionellosis and Chemokine signaling pathway. Our study firstly identified the possible associated factors with OP in the patients with CG, and mined the core genes and related pathways that could be used as biomarkers or potential therapeutic targets to reveal the shared mechanisms.

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“…Soluble CD14 was strongly associated with both BMD loss and hip fracture, and has recently been shown to be associated with hip fracture in the Cardiovascular Health Study. (34) CD14 is ubiquitously expressed (35) and, with IL-1b, is responsible for LPSmediated bone resorption. (36) Expression of CD14 was also shown to be higher in osteoporotic bone than control bone.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics

Nielson

Wiedrick

Shen

et al. 2017

Journal of Bone and Mineral Research

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Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men Study (MrOS) comprises men ≥65 in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multi-dimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4.6 years for changes in femoral neck bone mineral density (BMD) and for incident hip fracture. Change in BMD was determined from mixed effects regression models taking age and weight into account. Participants were categorized into three groups: BMD maintenance (no decline; estimated change ≥ 0 g/cm2, n=453); expected loss (estimated change 0 to 1 SD below the estimated mean change, −0.034 g/cm2 for femoral neck, n=1184); and accelerated loss (estimated change ≥ 1 SD below mean change, n=237). Differential abundance values of 3,946 peptides were summarized by meta-analysis to determine differential abundance of each of 339 corresponding proteins for accelerated BMD loss vs maintenance. Using this meta-analytic standardized fold change at cutoffs of ≥ 1.1 or ≤ 0.9 (p < 0.10), 20 proteins were associated with accelerated BMD loss. Associations of those 20 proteins with incident hip fracture were tested using Cox proportional hazards models with age and BMI adjustment in 2473 men. Five proteins were associated with incident hip fracture (HR between 1.29 and 1.41 per SD increase in estimated protein abundance). Some proteins have been previously associated with fracture risk (e.g., CD14 and SHBG), while others have roles in cellular senescence and aging (B2MG and TIMP1) and complement activation and innate immunity (CO7, CO9, CFAD). These findings may inform development of biomarkers for future research in bone biology and fracture prediction.

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Soluble CD14 and fracture risk

Cited by 7 publications

References 56 publications

Menopause and estrogen associations with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV

Menopause and estrogen associations with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV

Clinical features and shared mechanisms of chronic gastritis and osteoporosis

Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics

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