Association Between Bone Mineral Density, Bone Turnover Markers, and Serum Cholesterol Levels in Type 2 Diabetes

Purpose: The association between bone mineral density (BMD), bone turnover markers, and serum cholesterol in healthy population has already been proved. However, in patients with type 2 diabetes mellitus (T2D), it has not been adequately analyzed. In this study, we investigated the correlation between BMD, bone turnover markers, and serum cholesterol levels in people with T2D.Methods: We enrolled 1,040 men and 735 women with T2D from Zhongshan Hospital between October 2009 and January 2013. Their general condition, history of diseases and medication, serum markers, and BMD data were collected. We used logistic regression analysis to identify the association between serum cholesterol levels and BMD as well as bone turnover markers.Results: In multivariate regression analysis, we observed that in men with T2D, high high-density lipoprotein-cholesterol and total cholesterol levels were significantly associated with low total lumbar, femur neck, and total hip BMD, while low-density lipoprotein-cholesterol level was only inversely associated with total lumbar and femur neck BMD. Total cholesterol and low-density lipoprotein-cholesterol levels were also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and β-crosslaps. In women with T2D, high-density lipoprotein-cholesterol level was observed to be negatively correlated with total lumbar, femur neck, and total hip BMD, while total cholesterol and low-density lipoprotein-cholesterol levels were only associated with BMD at the total lumbar. Furthermore, total cholesterol was also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and β-crosslaps; high-density lipoprotein-cholesterol was only related to osteocalcin and parathyroid hormone, while low-density lipoprotein-cholesterol was only related to β-crosslaps in women.Conclusion: Our study suggests a significantly negative correlation between serum cholesterol levels and BMD in both men and women with T2D. The associations between serum cholesterol levels and bone turnover markers were also observed in T2D patients

On an Impulsive Food Web System with Mutual Interference and Distributed Time Delay

In this paper, we present a predator-prey system with mutual interference and distributed time delay and study its dynamical behavior. Based on the existence and universality of mutual interference among species, it is necessary to further study an impulsive food web system. By using stability theory, slight perturbation technique, and comparison theorem, we obtain some theoretical results of the system, such as boundedness and permanence. Moreover, numerical experiments are used to verify the theoretical results and to explore the dynamical behavior of the system, which exhibits rich dynamical behavior such as chaotic oscillation, periodic oscillation, symmetry-breaking bifurcations, chaotic crises, and period bifurcation. Finally, we give some practical guidelines for biological systems based on the theoretical results and numerical experiments of the system

CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury

Abstract In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers to the relationship between lung inflammatory diseases (COPD, asthma, and cystic fibrosis) and bone diseases, including osteopenia/osteoporosis. Compared to chronic lung diseases, the influence of ALI on the skeleton has not been investigated until now. Therefore, we investigated the effect of ALI on bone phenotypes in mice to elucidate the underlying mechanisms. In vivo bone resorption enhancement and trabecular bone loss were observed in LPS-induced ALI mice. Moreover, chemokine (C-C motif) ligand 12 (CCL12) accumulated in the serum and bone marrow. In vivo global ablation of CCL12 or conditional ablation of CCR2 in bone marrow stromal cells (BMSCs) inhibited bone resorption and abrogated trabecular bone loss in ALI mice. Furthermore, we provided evidence that CCL12 promoted bone resorption by stimulating RANKL production in BMSCs, and the CCR2/Jak2/STAT4 axis played an essential role in this process. Our study provides information regarding the pathogenesis of ALI and lays the groundwork for future research to identify new targets to treat lung inflammation-induced bone loss

Sox9 gene transfer enhanced regenerative effect of bone marrow mesenchymal stem cells on the degenerated intervertebral disc in a rabbit model.

OBJECTIVE: The effect of Sox9 on the differentiation of bone marrow mesenchymal stem cells (BMSCs) to nucleus pulposus (NP)-like (chondrocyte-like) cells in vitro has been demonstrated. The objective of this study is to investigate the efficacy and feasibility of Sox9-transduced BMSCs to repair the degenerated intervertebral disc in a rabbit model. MATERIALS AND METHODS: Fifty skeletally mature New Zealand white rabbits were used. In the treatment groups, NP tissue was aspirated from the L2-L3, L3-L4, and L4-L5 discs in accordance with a previously validated rabbit model of intervertebral disc degeneration and then treated with thermogelling chitosan (C/Gp), GFP-transduced autologous BMSCs with C/Gp or Sox9-transduced autologous BMSCs with C/Gp. The role of Sox9 in the chondrogenic differentiation of BMSCs embedded in C/Gp gels in vitro and the repair effect of Sox9-transduced BMSCs on degenerated discs were evaluated by real-time PCR, conventional and quantitative MRI, macroscopic appearance, histology and immunohistochemistry. RESULTS: Sox9 could induce the chondrogenic differentiation of BMSCs in C/Gp gels and BMSCs could survive in vivo for at least 12 weeks. A higher T2-weighted signal intensity and T2 value, better preserved NP structure and greater amount of extracellular matrix were observed in discs treated with Sox9-transduced BMSCs compared with those without transduction. CONCLUSION: Sox9 gene transfer could significantly enhance the repair effect of BMSCs on the degenerated discs

Safranin O staining of sections from the 5 groups at 6 (A–J) and 12 weeks (K–T) post-transplantation.

<p>Scale bar = 200 μm.</p

Imaging studies.

<p>(A) T2-weighted images of the treated discs (outlined by the red box) and adjacent control discs at 6 and 12 weeks post-transplantation. (B) The mean T2 of NP at 6 and 12 weeks post-transplantation. *P<0.05, #P<0.01 vs. the Sox9 group. Coronal and sagittal CT reconstruction images for the GFP (C) and Sox9 (D) groups.</p

Histological grading scale by Masuda et al [31].

<p>Histological grading scale based on four categories of degenerative changes. A normal disc is defined as 4 points. A higher score implies more severe degeneration in nucleus pulposus and annulus fibrosus.</p

Sox9-transduced BMSCs in monolayer.

<p>(A) P3 BMSCs exhibited a uniform fibroblast-like shape, and fluorescence microscopy showed Sox9 transduction efficiency at days 3, 7 and 14. (B) Sox9 expression was evaluated by western blot at days 3, 7, 10 and 14 after transduction. (C) Real-time PCR for the expressions of <i>Sox9</i>, <i>Aggrecan</i>, <i>Col II</i>, <i>Col I</i> and <i>Col X</i> was performed at day 21 after transduction using <i>GAPDH</i> as a housekeeping gene. All results represent the mean±SD of triplicate samples. *<i>P</i><0.05, #<i>P</i><0.01. Scale bar = 200 μm.</p