Serum CX3CL1/fractalkine concentrations are positively associated with disease severity in postmenopausal osteoporotic patients.

BACKGROUND: The chemokine (C-X3-C motif) ligand 1 (CX3CL1), also called fractalkine (FKN), has recently been reported to be involved in osteoclastogenic process and pathological bone destruction. OBJECTIVE: This study aimed to investigate the link between serum CX3CL1/FKN levels with disease progression of postmenopausal osteoporotic patients. METHODS: A total of 53 women with postmenopausal osteoporosis (PMOP group), 51 postmenopausal non-osteoporotic female patients (PMNOP group) and 50 premenopausal non-osteoporotic healthy women of childbearing age (control group) were enrolled in the study. The bone mineral density (BMD) for all subjects was determined via dual-energy X-ray absorptiometry of the lumbar spine, femoral neck, internal trochanter, total hip, greater trochanter and Ward's triangle. The levels of FKN in the serum were examined using the enzyme-linked immunosorbent assay method. The serum bone resorption markers TRACP-5b, NTX levels, inflammation markers IL-1ß and IL-6 as well as oestrogen-2(E2) were also detected in all participants. The visual analogue scores (VAS) and Oswestry Disability Index (ODI) for low back pain were recorded in PMOP females for evaluation of osteoporotic pain and function. RESULTS: FKN levels were significantly higher in postmenopausal osteoporotic patients compared with postmenopausal non-osteoporotic females (139.8 ± 44.3 pg/mL VS 116.5 ± 23.1 pg/mL, p < 0.05) and healthy controls (139.8 ± 44.3 pg/mL VS 109.7 ± 19.4 pg/mL, p < 0.05). Serum FKN concentrations were negatively associated with BMD at femoral neck (r = -0.394, p = 0.004), total hip(r = -0.374, p = 0.006), internal trochanter(r = -0.340, p = 0.013), greater trochanter(r = -0.376, p = 0.006), Ward's triangle(r = -0.343, p = 0.012), L1-L4 lumbar spine(r = -0.339, p = 0.013) and positively associated with VAS (r = 0.321, p = 0.019) and ODI (r = 0.377, p = 0.005) scores, bone turnover makers (TRACP-5b:r = 0.341, p = 0.012; NTX:r = 0.364, p = 0.007)as well as inflammation markers (IL-1ß: r = 0.396, p = 0.003; IL-6:r = 0.355, p = 0.009) in postmenopausal osteoporotic patients. CONCLUSIONS: Serum FKN may serve as a novel biomarker for assessing disease progression and a new potential therapeutic target for anti-resorptive treatment in osteoporosis patients.

Endogenous CSE/H2 S system mediates TNF-α-induced insulin resistance in 3T3-L1 adipocytes.

Tumour necrosis factor-α (TNF- α)is a major contributor to the pathogenesis of insulin resistance associated with obesity and type 2 diabetes. It has been found that endogenous hydrogen sulfide (H2 S) contributes to the pathogenesis of diabetes. We have hypothesized that TNF-α-induced insulin resistance is involved in endogenous H2 S generation. The aim of the present study is to investigate the role of endogenous H2 S in TNF-α-induced insulin resistance by studying 3T3-L1 adipocytes. We found that treatment of 3T3-L1 adipocytes with TNF-α leads to deficiency in insulin-stimulated glucose consumption and uptake and increase in endogenous H2 S generation. We show that cystathionine γ-lyase (CSE) is catalysed in 3T3-L1 adipocytes to generate H2 S and that CSE expression and activity are upregulated by TNF-α treatment. Inhibited CSE by its potent inhibitors significantly attenuates TNF-α-induced insulin resistance in 3T3-L1 adipocytes, whereas H2 S treatment of 3T3-L1 adipocytes impairs insulin-stimulated glucose consumption and uptake. These data indicate that endogenous CSE/H2 S system contributes to TNF-α-caused insulin resistance in 3T3-L1 adipocytes. Our findings suggest that modulation of CSE/H2 S system is a potential therapeutic avenue for insulin resistance.