Association between thyroid hormones and skeletal muscle and bone in euthyroid type 2 diabetes patients.

Background: The impact of thyroid hormones within their normal ranges on skeletal muscle and bone in patients with type 2 diabetes mellitus (T2DM) remains unknown. The purpose of this study was to investigate the relationships of thyroid hormones with muscle and bone in euthyroid patients with T2DM. Methods: This cross-sectional study included 344 euthyroid T2DM patients. Muscle mass and bone mineral density were measured by dual-energy X-ray absorptiometry. The levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxin (FT4) were measured by electrochemiluminescence immunoassay. Results: The results revealed that FT3 was positively correlated with body mass index (BMI) in male patients after age correction. In men, FT4 was negatively correlated with body weight, BMI, total muscle mass, appendicular skeletal muscle mass (ASM), and ASM index (ASMI), while FT3/FT4 was positively correlated with body weight, BMI, total muscle mass, ASM, and ASMI after age correction. In women, FT4 was negatively correlated with ASM and ASMI, while FT3/FT4 was positively correlated with ASM and ASMI after age correction. FT3/FT4 was significantly lower in men with low muscle mass than in those with normal muscle mass. The age-adjusted odds for incident low muscle mass comparing the lowest and highest FT3/FT4 increased in men. Conclusions: FT3/FT4 was positively correlated with ASM and ASMI in both men and women. Therefore, FT3/FT4 may be a parameter indicative of low muscle mass in euthyroid men with T2DM.

Association of Hydrogen Sulfide with Femoral Bone Mineral Density in Osteoporosis Patients: A Preliminary Study.

BACKGROUND Accumulated evidence has suggested that hydrogen sulfide (H2S) has a role in bone formation and bone tissue regeneration. However, it is unknown whether the H2S content is associated with bone mineral density (BMD) in patients with osteopenia/osteoporosis. MATERIAL AND METHODS In the present study, we aimed to explore the changes of serum H2S in osteopenia and osteoporosis patients. We analyzed femur expression of cystathionine ß synthase (CBS), cystathionine γ lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), which are key enzymes for generating H2S. RESULTS Sixteen (16%) patients had osteopenia, 9 (9%) had osteoporosis, and 75 (75%) had normal BMD. In comparison with patients with normal BMD (controls), the serum levels of H2S were unexpectedly increased in patients with osteopenia and osteoporosis. This increase was much higher in patients with osteoporosis than in those with osteopenia. Serum H2S levels were negatively correlated with femoral BMD, but not lumbar BMD. Interestingly, the expression of CBS and CSE were downregulated in femur tissues in patients with osteoporosis, whereas the expression of 3-MST remained unchanged. Serum phosphorus levels, alkaline phosphatase, hemoglobin, and triglycerides were found to be closely associated with CBS and CSE scores in femur tissues. CONCLUSIONS Serum H2S levels and femur CBS and CSE expression may be involved in osteoporosis pathogenesis.

Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease.

Angiopoietin-like protein 2 (ANGPTL2) stimulates inflammation and is important in the pathogenesis of diabetic kidney disease (DKD). Irbesartan is helpful in reducing diabetes-induced renal damage. In this study, the effects of irbesartan on DKD and its renal protective role involving ANGPTL2 in DKD rats were examined. Wistar rats were divided into normal, DKD, and DKD + irbesartan groups. The DKD + irbesartan group was treated once daily for 8 weeks with 50 mg/kg irbesartan via intragastric gavage. The 24-h urinary albumin was determined each week, renal pathological changes were observed, and expression of ANGPTL2 and nuclear factor-kappa B (NF-κB) in rat renal tissue was assessed by immunohistochemistry. Mouse podocytes cultured in a high concentration of glucose were classified into four groups based on the irbesartan concentrations (0, 25, 50, and 75 ºg/mL). Expression of ANGPTL2 and phosphorylated IκB-α was assessed by Western blotting. The mRNA levels of ANGPTL2 and monocyte chemotactic protein 1 (MCP-1) were assessed by real-time polymerase chain reaction. The DKD rats displayed proteinuria, podocyte injury, and increased ANGPTL2 and NF-κB expression. All were relieved by irbesartan treatment. In podocytes cultured in elevated glucose, ANGPTL2 and phosphorylated IκB-α were overexpressed at the protein level, and ANGPTL2 and MCP-1 were highly expressed at the mRNA level. Irbesartan down-regulated ANGPTL2 and phosphorylated IκB-αexpression at the protein level and inhibited ANGPTL2 and MCP-1 expression at the mRNA level. The ameliorative effects of irbesartan against DKD involves podocyte protection and suppression of ANGPTL2.

Quantitative associations between osteocyte density and biomechanics, microcrack and microstructure in OVX rats vertebral trabeculae.

Osteocytes actively regulate bone modeling and remodeling, direct skeletal mineralization, and regulate calcium/phosphate homeostasis and extracellular matrix metabolism; yet the specific role of osteocytes in maintaining bone structural integrity and strength is unknown. Studies have shown that the density of osteocytes decreases with age and estrogen deficiency, as seen in postmenopausal women. Here, we examined the relationships between osteocyte density and the related variables, including biomechanics, bone mineral density, microcrack and microstructure of vertebral trabeculae, in ovariectomized rats. We found that osteocyte density correlated with some of the parameters that determine the biomechanical quality of bone. Our findings suggest that osteocytes could play a crucial role in maintaining the mechanical quality of bone, and osteocyte density could be considered as an alternative index in assessing bone quality.

[Nanomechanical properties of vertebral trabeculae in ovariectomized rats].

OBJECTIVE: To study the nanomechanical properties of the vertebral trabeculae of ovariectomized rat using nanoindentation. METHODS: Twenty 10-month-old SD rats were randomly divided into 2 equal groups: ovariectomized (OVX) group and Sham operation (SHAM) group. Fifteen weeks post-operationally dual energy X-ray absorptiometry was used to measure the bone mineral density (BMD) of the total body and of the sixth lumbar vertebra. Then the rats were killed. The BMD values of the sixth lumbar vertebrae were measured by DXA. Bone histomorphometry was performed on the proximal metaphysis of the right tibia. Three of the sixth lumbar vertebrae were randomly selected from each group and embedded in methyl methacrylate. Each vertebra was cut into two parts along the transverse direction in the middle point of longitudinal axis so as to expose the trabeculae on the cross section. The lower part was polished, trabeculae were randomly selected from 4 places, and 5 points from each place were randomly selected to undergo nanoindentation so as to measure the nanomechanical properties. RESULTS: Compared with the SHAM rats, the BMD of the sixth lumbar vertebra of the OVX rats was reduced significantly (P < 0.05). The histomorphometry of the tibia showed an increase in trabecular separation and a decrease in trabecular bone area fraction (both P < 0.05); the trabecular number and thickness decreased in these 2 groups, however, without significant difference between them. Nanoindentation tests showed that the values of hardness and elastic modulus of the trabeculae of the OVX rats were 0.91 GPa +/- 0.13 GPa and 21.01 GPa +/- 2.48 GPa respectively, not significantly different from those of the SHAM rats, 0.90 GPa +/- 0.09 GPa and 22.03 GPa +/- 2.44 GPa respectively. CONCLUSION: A novel technique, nanoindentation is able to directly measure the nanomechanical properties of trabeculae. Estrogen deficiency after ovariectomy induces significant osteoporotic change, but has no significant influence on the trabecular nanomechanical properties.