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Osteoarthritis (OA) is the most common cause of musculoskeletal disability and pain in the world. The current drug treatment for OA is symptom relieving, and there is an urgent need for treatments that could retard, prevent or repair cartilage destruction in OA. Obesity is a major risk factor for OA. Traditionally, it has been thought to contribute to the development of OA by increasing the load on weight-bearing joints. However, this appears to be an over-simplification, because obesity is also linked to OA in the hand and finger joints. Recent studies have shown that adipocytokine leptin is a possible link between obesity and OA: Leptin levels in synovial fluid are increased in obese patients, leptin receptor (Ob-R) is expressed in cartilage, and leptin induces the production of matrix metalloproteinases (MMPs), pro-inflammatory mediators and nitric oxide (NO) in chondrocytes. Furthermore, according to the very recent findings, not only leptin levels in the joint but also leptin sensitivity in the cartilage are enhanced in obese OA patients. The findings supporting leptin as a causative link between obesity and OA offer leptin as a potential target to the development of disease-modifying drugs for osteoarthritis (DMOAD), especially for obese patients.

Summary Background Maternal diabetes interferes with fetal lung development and postnatal treatments may further disturb pulmonary growth. Therefore, we investigated the effect of postnatal oxygen exposure on alveolar development in neonatal rat lungs pre-exposed to intrauterine hyperglycemia. Methods Diabetes was induced in Sprague-Dawley rats with streptozotocin injection before pregnancy. Hyperglycemia-exposed and control litters were randomized to breath room air or 85% oxygen for 7 days after birth. Lungs were analyzed on postnatal d7 for weight, morphology, apoptosis, proliferation, and biomarkers of oxidative stress. Results Maternal hyperglycemia accelerated lung development as demonstrated by thinner alveolar walls and slightly increased secondary septation when compared to room air bred rats. Hyperoxia alone caused thin-walled and enlarged alveoli with few secondary septa. Interestingly, the dual exposure inhibited the thinning of alveolar walls and the disappearance of mesenchymal cells from the alveolar walls together with the delay in the formation of alveoli and secondary crests. While the lungs' oxidative stress was similar in all groups, pulmonary apoptosis and proliferation were altered. Conclusion Our results thus indicate that the hyperglycemic priming of the fetal lung modifies the deleterious effect of hyperoxia on alveolarization in neonatal rats. Pediatr Pulmonol. 2014; 49:179–188. © 2013 Wiley Periodicals, Inc.