Formation of advanced glycation end products (AGEs) in extracellular matrix (ECM) is implicated in the development of chronic diabetic complications. However, the involvement of AGEs in diabetic bone disease has not been well established. We have examined whether AGEs are increased in the bone collagen of streptozotocin-induced diabetic rats in vivo and whether glycation of type I collagen affects the functions of osteoblastic cells in vitro. During 12 weeks of observation, AGEs in collagen extracted from the tibiae of diabetic rats increased in a time-dependent manner and were significantly higher than controls at every time point. In vitro, the incubation of collagen with glucose-6-phosphate resulted in a time-dependent increase of AGEs. When osteoblastic cells isolated from fetal rat calvaria were cultured on AGE-modified type I collagen, it dose-dependently inhibited phenotypic expressions of osteoblasts. Among osteoblastic parameters, nodule formation was the most sensitive, being inhibited by approximately 70% by the glycation of collagen for only 1 week. Alkaline phosphatase activity and osteocalcin secretion were inhibited by 20-30% and 15-70%, respectively, by the glycation of collagen for 1-5 weeks. These results indicate that AGE-modified collagen affects osteoblastic cell differentiation and function in vitro and suggest that similar changes occurring in vivo may contribute to diabetic osteopenia.

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Many risk factors for asthma have been proposed including age, gender (male), smoking, and family history of asthma. The importance of breastfeeding to childhood asthma is a controversial issue. The present study investigated the relation between breastfeeding and the prevalence of asthma among a childhood population. The subjects were 25,767 students, representing all public elementary and junior high schools in Tokorozawa, Japan (age range, 6--15 years). The study population included 2,315 students with asthma and 21,513 controls. Participants' parents completed the Japanese version of the American Thoracic Society and Division of Lung Diseases, National Heart, Lung, and Blood Institute, questionnaire for children adopted by the Japanese Environmental Agency in 1998. The authors added supplementary questions on the parental history of asthma and feeding patterns from the age of 0--3 months. The risk of breastfeeding for asthma was compared with that of artificial feeding. After adjustment for age, gender, parental smoking status, and parental history of asthma, a significantly higher prevalence of asthma was noted among children who had been breastfed (adjusted odds ratio = 1.198; 95% confidence interval: 1.054, 1.363; p for trend < 0.01). The results indicated that breastfeeding in infancy might be related to the higher prevalence of asthma during preadolescence.

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We previously reported that mouse mammary carcinoma cell lines (MMT060562 and BALB/c-MC) induced osteoclast formation through production of prostaglandin E 2 (PGE 2 ) in cocultures with mouse bone marrow cells, but the mechanism(s) of PG production remained unclear. In the present in vitro and in vivo studies, we tested the involvement of cyclo