An osteoarthritis triple play

Abstract

In American baseball, a triple play is the rare act of making three outs during the same continuous play. In this issue of J Mol Med, we feature a triple play against the world's most common disease. Osteoarthritis (OA) is a degenerative joint disease and the commonest form of arthritis affecting about one third of adults over age 45 years. Since most of these persons seek medical treatment, osteoarthritis is a massive worldwide healthcare and financial burden. Articular cartilage loss, subchondral bone thickening, and osteophyte formation characterize the condition. A cartoon outlining the process is shown (Fig. 1). While new targets are emerging to treat osteo-arthritis [1], palliative treatments with non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroid injections remain the most common therapies. Eventually, hip and knee replacement become necessary in many patients. Furthermore, much back surgery is a sequel to OA. Not uncommonly, physicians prescribe opioids, such as oxycodone when NSAIDs fail. As a result, osteoarthritis is a major contributor to the entire pain industry.OA is associated with many contributing factors including aging, obesity, trauma, genetics, and other accompanying causes; however, basic molecular mechanisms are not fully understood. Debate remains as to what is really the precipitating pathology, since everyone eventually has OA. Poulet and Staines have underscored the focus on different joint tissues affected by OA, including a focus on articular cartilage maintenance, targeting subchondral bone, inhibiting osteoclast activity, modifying osteoblast behavior, and adjusting angiogenesis [2].Moon et al. recently reported in this journal that mice lacking pannexin 3 (Panx3) specifically in cartilage were markedly resistant to the development of OA following destabilization after medial meniscus surgery [3]. Their data indicated a specific catabolic role of Panx3 in articular cartilage maintenance and identified Panx3 as a potential therapeutic target for OA. Their report was the first in vivo evidence for a role of Panx3 in disease. Since three additional investigations into OA are reported by this journal following the paper by Moon and colleagues, examining the subject again appears highly justified.Ko and colleagues also concerned themselves with articular cartilage maintenance [4]. They point out that heat-shock proteins (HSPs), intracellular chaperones, orchestrate tissue homeostasis and are important in remodeling and repair. They studied the articular cartilage from OA patients undergoing knee surgery and found reduced HSP60 concentrations in cartilage and synovial fluid compared to specimens from non-OA patients. Furthermore, expression of the SRY-box 9 (SOX9) chondrogenic transcription factor was reduced. They next investigated chondrocyte cultures that were stimulated with interleukin-1β (IL-1β). This exposure reduced HSP60, SOX9, collagen II, and aggrecan expression; however, the reductions were ameliorated when HSP60 was restored. To pursue the issue further, the i...

The Role of Pannexin 3 in Bone Biology

“…Other pathways are also reported. For example, Wnt/β-catenin signaling activates bone morphogenetic protein-2 (BMP2) expression (Luft 2016). BMP-2 activates nuclear factor of activated T-cells calcineurin-dependent 1 (NFATc1) through an autoregulatory loop involving Smad/Akt/Ca 2++ signaling (Moon et al 2015).…”