High-mobility group box 1 protein induces epithelialmesenchymal transition in upper airway epithelial cells.

BACKGROUND: In the treatment of rhinosinusitis, nasal polyps are a major problem, and the epithelial-to-mesenchymal transition (EMT) process is considered pivotal in their development. Although various studies have addressed the role of high mobility group box 1 (HMGB1) nuclear protein in this setting, its impact on EMT has yet to be evaluated. Our aim was the pathogenic mechanism of HMGB1 in EMT and EMT-induced upper respiratory nasal polyps. METHODS: We investigated the EMT-related effects of HMGB1 in human nasal epithelial (HNE) cells using western blot analysis, transepithelial-electrical resistance (TEER) testing, wound healing assay, and immunofluorescence. HNE cells were incubated in a low-oxygen environment to evaluate the role of HMGB1 in hypoxia-induced EMT. Further support for our in vitro findings was obtained through murine models. Human nasal polyps and nasal lavage fluid samples were collected for western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: HMGB1 increased mesenchymal markers and decreased epithelial markers in HNE cells. Hypoxia-induced HMGB1 in turn induced EMT, apparently through RAGE signaling. We verified HMGB1-induced EMT in the upper respiratory epithelium of mice by instilling intranasal HMGB1. In testing of human nasal polyps, HMGB1 and mesenchymal markers were heightened, whereas epithelial markers were reduced, compared with tissue controls. CONCLUSION: HMGB1 secretion in nasal epithelium may be a major pathogenic factor in upper respiratory EMT, contributing to nasal polyps.

Higher serum uric acid is associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in healthy postmenopausal women.

UNLABELLED: Higher serum uric acid (UA) was associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in postmenopausal women. Furthermore, UA suppressed osteoclastogenesis and decreased production of reactive oxygen species in osteoclast precursors, indicating UA may have beneficial effects on bone metabolism as an antioxidant. INTRODUCTION: UA is known to play a physiological role as an antioxidant, and oxidative stress has detrimental effects on bone metabolism. In the present study, we investigated the association of serum UA level with the osteoporosis-related phenotypes and its direct effect on bone-resorbing osteoclasts using in vitro systems. METHODS: This is a large cross-sectional study, including 7,502 healthy postmenopausal women. Bone mineral density (BMD) and serum UA concentrations were obtained from all subjects. Data on bone turnover markers and lateral thoracolumbar radiographs were available for 1,023 and 6,918 subjects, respectively. An in vitro study investigated osteoclastogenesis and reactive oxygen species (ROS) levels according to UA treatment. RESULTS: After adjusting for multiple confounders, serum UA levels were positively associated with BMD at all sites (all p < 0.001). Compared with the participants in the highest UA quartile, the odds for osteoporosis were 40 % higher in those in the lowest quartile. The serum UA levels were inversely related to both serum C-terminal telopeptide of type I collagen and osteocalcin levels (p < 0.001 and p = 0.004, respectively). Consistently, subjects with vertebral fracture had lower serum UA levels, compared with those without it (p = 0.009). An in vitro study showed that UA decreased osteoclastogenesis in a dose-dependent manner and reduced the production of ROS in osteoclast precursors. CONCLUSION: These results provide epidemiological and experimental evidence that serum UA may have a beneficial effect on bone metabolism as an antioxidant in postmenopausal women.

Association between metabolic syndrome and bone loss at various skeletal sites in postmenopausal women: a 3-year retrospective longitudinal study.

UNLABELLED: Although the presence of metabolic syndrome (MetS) and increasing numbers of MetS components were associated with attenuated bone loss at various skeletal sites in postmenopausal women, this beneficial effect of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects. INTRODUCTION: Previous cross-sectional epidemiological studies reported the inconsistent results regarding the combined effects of MetS on bone mass. In our present report, we performed a large, longitudinal study to evaluate MetS in relation to annualized bone mineral density (BMD) changes in postmenopausal Korean women. METHODS: The study cohort consisted of 1,218 postmenopausal women who had undergone comprehensive routine health examinations with an average follow-up interval of 3 years. The BMD at the lumbar spine and proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and at follow-up. RESULTS: Following adjustment for age, baseline BMD, and lifestyle factors, the women with MetS had 21.7, 17.0, 26.7, and 31.1 % less bone loss at the total femur, femur neck, trochanter, and lumbar spine, respectively, compared with MetS-free women (P = 0.004 to 0.041). Consistently, the rates of bone loss at all skeletal sites were linearly attenuated with increasing numbers of MetS components (P = 0.004 to <0.001). Importantly, when weight and height were added as confounding factors, the differences and trends of annualized BMD changes according to the MetS status disappeared. CONCLUSION: Our current results indicate that the beneficial effects of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects. Consequently, MetS per se may not be a meaningful concept for predicting future bone loss and for explaining associations between osteoporosis and cardiovascular diseases.

The association between serum osteocalcin levels and metabolic syndrome in Koreans.

UNLABELLED: The association between serum osteocalcin levels and metabolic syndrome (MS) in Korean individuals was investigated. Serum osteocalcin levels are significantly lower in subjects with MS than in those without the disease, regardless of glucose metabolism. INTRODUCTION: Osteocalcin was recently shown to affect energy metabolism. In the present study, we investigated the possible association between serum osteocalcin concentrations and MS. METHODS: A cross-sectional community-based survey was conducted. Serum osteocalcin, type 1 collagen C-telopeptide (CTX) and total alkaline phosphatase (ALP) concentrations were determined in 567 subjects. MS was defined according to NCEP-ATP III criteria. RESULTS: Serum osteocalcin concentrations were significantly lower in subjects with MS than those without MS in postmenopausal women (18.923 ± 7.685 vs 22.513 ± 7.344 ng/ml, P<0.001) and marginally lower in subjects with MS than those without MS in men (14.550 ± 5.090 vs 16.125 ± 4.749 ng/ml, P=0.086) after adjustment for age and BMI. Further controlling with CTX or ALP did not affect this association in postmenopausal women; however, controlling with osteocalcin abolished the association between CTX and MS. Significant differences in serum osteocalcin levels by MS status were noted in subjects with normal glucose tolerance as well as those with abnormal glucose tolerance (P=0.032 and P<0.001, respectively). Compared with subjects with the highest quartile of osteocalcin, those in the lower quartile groups (Q1-Q3) had significantly increased risks of MS (ORs=5.18, CIs=1.15-23.42) in men. In postmenopausal women, the ORs for MS were significantly higher in the lowest quartile than in the highest quartile (ORs=5.25, CIs=2.42-11.36). CONCLUSIONS: These findings suggest that osteocalcin is associated with MS, independently of glucose metabolism.

Atypical endoscopic features of rectal carcinoids.

BACKGROUND AND STUDY AIMS: It is not normally difficult to diagnose carcinoid tumors (well-differentiated endocrine neoplasms) of the rectum endoscopically, as they usually have a characteristic appearance. However, little is known about the atypical endoscopic findings in some rectal carcinoids and the present study was performed to analyze these. PATIENTS AND METHODS: The endoscopic findings in 67 consecutive patients with rectal carcinoids (37 men, 30 women; age range 23 - 76) were analyzed retrospectively. RESULTS: Tumor size ranged from 2 mm to 30 mm (average 7.4 mm). Of the 67 patients, 52 (78 %) displayed the characteristic endoscopic findings of smooth, round, sessile elevations covered with normal-appearing or yellow-discolored mucosa; in 15 (22 %) there were one or more atypical endoscopic findings. These included a semipedunculated appearance (n = 6), hyperemia (n = 5), a central depression (n = 6), erosion (n = 5), and ulceration (n = 4). Atypical findings were noted in none of 20 carcinoids &lambda< 5 mm in diameter; in six (20 %) of the 30 carcinoids between 5 mm and 9 mm; in six (43 %) of the 14 carcinoids between 10 mm and 19 mm; and in three (100 %) of the three carcinoids >/= 20 mm in diameter ( P < 0.001). Invasion into the muscularis propria or metastasis to the liver or lymph nodes occurred in three of the four patients with ulceration, but it was confirmed in only one of the 63 patients without ulceration ( P < 0.001). CONCLUSIONS: Atypical endoscopic appearances of rectal carcinoids are observed more frequently as the size of the tumor increases and a finding of ulceration may have a prognostic value.