Osteoarthritis year 2011 in review: biology

Abstract

This review is focused on advances in understanding the biology of joint homeostasis and osteoarthritis (OA) pathogenesis mechanisms that have led to proof of concept studies on new therapeutic approaches. The three selected topics include angiogenesis in joint tissues, biomechanics and joint lubrication and mitochondrial dysfunction. This new information represents progress in the integration of mechanisms that control multiple aspects of OA pathophysiology.

Fig. 1. Dysfunctional mitochondria in OA pathogenesis

Multiple factors contribute to mitochondrial dysfunction, including inhibition of mitochondrial biogenesis through suppression of key mitochondrial transcription factors PGC. Risk for mitochondrial dysfunction is also increased in individuals with certain mitochondrial DNA haplotypes and through acquired mitochondrial DNA mutations. As a result of defective autophagy, dysfunctional mitochondria accumulate and produce increased amounts of reactive oxygen species, which promote inflammatory responses, abnormal gene expression and cell death. The impact of mitochondrial dysfunction is further aggravated by reduced levels of SOD2 and deficient anti-oxidant defenses.