Dataset Information

Anxa2 attenuates osteoblast growth and is associated with hip BMD and osteoporotic fracture in Chinese elderly.

ABSTRACT: Low bone mineral density (BMD) is a risk factor of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. It was known that PBM-expressed Anxa2 protein is associated with BMD, and extracellular Anxa2 protein promotes osteoclastogenesis. This study aimed to test 1) whether Anxa2 protein level in PBM differs significantly between subjects with OF and without fracture history (NF); 2) whether Anxa2 level in plasma is associated with BMD; 3) how Anxa2 protein at various concentrations would affect osteoblastic activity in vitro. All the study subjects were Chinese Han elderly. Firstly, Anxa2 protein in PBM was identified and quantitated by LC-MS/MS and compared between 45 OF cases and 42 healthy controls. Secondly, plasma Anxa2 protein level was quantitated by ELISA and compared between unrelated subjects with extremely low vs. high hip BMD (0.63±0.10 vs. 1.05±0.10 g/cm2, n = 75). Furthermore, in vitro functional assay was utilized to test the effects of extracellular Anxa2 protein on osteoblastic growth. We found that Anxa2 protein expression in PBM was significantly up-regulated in OF vs. NF subjects (fold change [FC)] = 1.16, P<0.05). Plasma Anxa2 protein concentration (range: 31.69-227.35ng/ml) was significantly elevated in low vs. high BMD subjects (84.85 vs. 66.15ng/ml, FC = 1.28, P<0.05). Cellular dynamical monitoring demonstrated that the general shape of dose-response relationship is the inverse U-shaped curve. Specifically, lower dose of Anxa2 protein may promote osteoblast growth and the optimal concentration for osteoblastic growth was around 50ng/ml, but even higher concentration could attenuate hFOB1.19 osteoprogenitor cell growth. We concluded that Anxa2 protein could attenuate osteoblast growth and be associated with hip BMD and OF in Chinese elderly.

SUBMITTER: Zhou X

PROVIDER: S-EPMC5865729 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Anxa2 attenuates osteoblast growth and is associated with hip BMD and osteoporotic fracture in Chinese elderly.

Zhou Xu X Wu Long-Fei LF Wang Wen-Yu WY Lu Xin X Jiang Zhen-Huan ZH Zhang Yun-Hong YH Jiang Ding-Hua DH Jiang Jian-Nong JN Gao Hong-Qing HQ Lei Shu-Feng SF Deng Fei-Yan FY

PloS one 20180323 3

Low bone mineral density (BMD) is a risk factor of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. It was known that PBM-expressed Anxa2 protein is associated with BMD, and extracellular Anxa2 protein promotes osteoclastogenesis. This study aimed to test 1) whether Anxa2 protein level in PBM differs significantly between subjects with OF and without fracture history (NF); 2) whether Anxa2 level in plasma is associated with BMD; 3) h ...[more]

PMID: 29570731

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Project description:BackgroundThe purpose of this study was to report the RNA sequencing profile according to the presence or absence of sarcopenia in elderly patients with osteoporotic hip fracture. Therefore, an important genetic factor candidate for sarcopenia causing hip fracture in elderly with osteoporosis has been identified.MethodsThe patient group involved subjects over 65 years who had undergone hip fracture surgery. Among 323 hip fracture (HF) patients identified from May 2017 to December 2019, 162 HF patients (90 non-sarcopenia and 72 sarcopenia groups), excluding subjects with high energy trauma and non-osteoporosis, were finally included in the analysis. For RNA sequencing, each patient with hand grip strength (HGS) values in the top 10% were enrolled in the control group and with the bottom 10% in the patient group. After excluding patients with poor tissue quality, 6 patients and 5 patients were selected for sarcopenia and non-sarcopenia groups, respectively. For qPCR validation, each patient with HGS values in the top 20% and bottom 20% was enrolled in the control and patient groups, respectively. After excluding patients with poor tissue quality, 12 patients and 12 patients were enrolled in the sarcopenia and non-sarcopenia groups, respectively. Sarcopenia was deﬁned according to the Asia Working Group for Sarcopenia (AWGS) criteria for low muscle strength (hand grip strength below 18 kg in women and 28 kg in men) and low muscle mass (SMI below 5.4 kg/m2 in women and 7.0 kg/m2 in men). The libraries were prepared for 100 bp paired-end sequencing using TruSeq Stranded mRNA Sample Preparation Kit (Illumina, CA, USA). The gene expression counts were supplied to Deseq2 to extract possible gene sets as differentially expressed genes (DEG) that discriminate between sarcopenia and non-sarcopenia groups that were carefully assigned by clinical observation. For the classification of the candidate genes from DEG analysis, we used the public databases; gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Quantitative real-time PCR was performed for validation.ResultsSamples collected were subjected to RNAseq using the Illumina platform. A total of 11 samples from both sarcopenia and non-sarcopenia groups were sequenced. Fifteen genes (RUNX 1, NGFR, CH3L1, BCL3, PLA2G2A, MYBPH, TEP1, SEMA6B, CSPG4, ACSL5, SLC25A3, NDUFB5, CYC1, ACAT1, and TCAP) were identified as differentially expressed genes (DEG) in both the groups.In the qPCR results, the expression levels of SLC25A3 and TCAP gene in the OS group were significantly lower than in the non-OS groups whereas an increase in RUNX1 mRNA level was observed in the OS samples (p < 0.05).ConclusionsIn summary, this study detected gene expression difference according to the presence or absence of sarcopenia in elderly osteoporosis female patients with hip fracture. We have also identified 15 important genes (RUNX 1, NGFR, CH3L1, BCL3, PLA2G2A, MYBPH, TEP1, SEMA6B, CSPG4, ACSL5, SLC25A3, NDUFB5, CYC1, ACAT1, TCAP), a few GO categories and biological pathways that may be associated with the osteosarcopenia. Our study may provide effective means for the prevention, diagnosis and treatment sarcopenia in elderly osteoporosis female patients.The translational potential of this articleThese findings provide a novel insight into the effects of aging on the response in women with postmenopausal osteoporosis. Further studies are underway to identify the specific signalling pathways involved. These results reveal potential therapeutic targets that could aid the regenerative capacity of aging skeletal muscle.

Project description:The osteoporotic hip fracture is associated with a high impact on morbidity, mortality, and health expenditure. The Chilean health system is made up of a mixed care system, with the public system called FONASA and the private system called ISAPRE. The people with lower incomes are listed on FONASA and correspond to 80.8% of the population. The aims of this study were to describe the incidence of hip fracture in the Chilean population from the age of 45 years and to estimate the direct medical cost of this disease. The records of the Department of the Health Statistics and Information of the Ministry of Health were used, from which the number of national hospital discharges due to hip fractures was obtained (codes S720, S721, and S722 of the ICD-10), in adults aged 45 years or older, by sex, from 2006 to 2017. The cost of osteoporotic hip fracture treatment in the public health system was obtained from the data of the surgical treatment according to the payment method associated with diagnosis (PAD bonus). A surgical intervention budget was used in a private clinic to calculate the direct cost of osteoporotic hip fracture in the private system. Between 2006 and 2017, the number of hospital discharges due to osteoporotic hip fracture in adults aged 45 years and older has increased progressively, registering 9.583 hospital discharges for this cause in 2017, which corresponds to 50% more than those recorded in 2006, with a 3?:?1 F/M ratio. The mean annual rate of hip fractures is 148.7 per 100,000 inhabitants aged above 45 years. The individual cost of managing an osteoporotic hip fracture in the public system was USD$ 3,919, and USD$ 9,092 in the private health system. The incidence of hip fracture was comparable with data from Southern European countries and from neighboring countries, such as Argentina and Uruguay. Hospitalization cost of hip fracture in Chile was 34 million USD per year. Hip fracture constitutes a serious healthcare problem in Chile, and efforts for the prevention and management of osteoporosis are needed.

Project description:BACKGROUND:It is known that mortality after hip fracture increases compared to the general population; the trend in mortality is a controversial issue. The objective of this study is to examine incidence, trends, and factors associated with mortality in patients with osteoporotic hip fractures. METHODS:This is a retrospective cohort study that uses the Registry for Hospital Discharges of the National Health System of our hospital. Patients older than 45 having an osteoporotic hip fracture between 1999 and 2015 were identified. Demographic data and comorbidities were obtained. A survival analysis was performed (Cox regression and Kaplan-Meier). Incidence rate, standardized death rate (SDR), trend (Poisson regression), and risk (hazard ratio) were calculated. RESULTS:During 1999-2015, in our hospital, there were a total of 3992 patients admitted due to osteoporotic hip fracture. Out of these 3992 patients, 3109 patients (77.9%) were women with an average age of 84.47 years (SD 8.45) and 803 (22.1%) were men with an average age of 81.64 years (SD 10.08). The cumulative incidence of mortality was 69.38%. The cumulative mortality rate for 12 months was 33%. The annual mortality was 144.9/1000 patients/year. The 1-year mortality rate increased significantly by 2% per year (IRR 1.020, CI95% 1.008-1.033). The median overall survival was 886 days (CI95% 836-951). The probability of mortality density for a period of 10 years following a hip fracture was 16% for women and 25% for men (first 90 days). The SDR was 8.3 (CI95% 7.98-8.59). Variables that showed statistically significant association with mortality were aged over 75, masculine, institutionalization, mild to severe liver disease, chronic kidney disease, COPD, dementia, heart failure, diabetes, the Charlson Index > 2 , presence of vision disorders and hearing impairment, incontinence, and Downton scale. CONCLUSIONS:For the last 17 years, an increase of mortality for patients with hip fracture and a higher mortality rate in men than in women were observed. Institutionalization combined with comorbidities is associated with a higher mortality.

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Dataset Information

Anxa2 attenuates osteoblast growth and is associated with hip BMD and osteoporotic fracture in Chinese elderly.

Publications

Anxa2 attenuates osteoblast growth and is associated with hip BMD and osteoporotic fracture in Chinese elderly.

Similar Datasets

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