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Extracellular pH proved Megestrol Acetate to more potently influence cell function than oxygen tension, the latter showing down-regulation of COL1 gene expression and up-regulation of VEGF protein under hypoxia. Hypoxic culture inhibits COL1 mRNA expression pH-dependently, while expression of SOX9 is largely hypoxia independent, but pH dependent. Expression of HIF1A and VEGF revealed divergent pH dependencies. Subtle fluctuations in extracellular pH and oxygen tension clearly influence chondrocyte metabolism and marker expression. Sophisticated pH and oxygen control not only allows study of (patho)physiological changes, but also opens new venues in cartilage tissue engineering. ? 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:537�C545, 2010 ""Bisphosphonates have been used for years to suppress bone turnover and reduce fracture risk. Bisphosphonates have recently been associated with atypical femoral http://www.selleckchem.com/products/birinapant-tl32711.html fractures, which are catastrophic, low trauma, brittle fractures that appear to occur more frequently than in untreated individuals. Previous work using a dog model has demonstrated bisphosphonate-induced reductions in bone toughness (the inverse of brittleness), yet data are lacking to show this occurs in rodents. The goal of this study was to determine if bisphosphonate-induced alterations in toughness could be quantified in rats. At 26 weeks of age, skeletally mature rats (n?=?32 total) were given an injection of either zoledronate (100?��g/kg body weight) or vehicle (0.5?ml saline). Five weeks post-injection, both femora were collected and analyzed for geometry and mechanical properties. To assess the effect of testing rate on the biomechanical outcomes, the left femora were broken at 2?mm/min, while the right femora were broken at 20?mm/min. The results showed a significantly lower energy to failure in zoledronate-treated animals compared to vehicle at the slow testing rate (?15%, p?selleck zoledronate only at the slow rate (?40%, p?
