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New targets for disease modifying osteoarthritis drugs: chondrogenesis and Runx1
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  1. Francisco J Blanco1,2,3,
  2. Cristina Ruiz-Romero1,4
  1. 1Rheumatology Division, INIBIC-Hospital Universitario A Coruña, A Coruña, A Coruña, Spain
  2. 2Universidad de Santiago de Compostela, A Coruña. Spain
  3. 3Red de Inflamación y Enfermedades Reumaticas (RIER)-Instituto de Salud Carlos III, Madrid, Spain
  4. 4CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain
  1. Correspondence to Dr Francisco J Blanco, Rheumatology Division, INIBIC-Hospital Universitario A Coruña, Xubias, 84, A Coruña, A Coruña 15006, Spain; fblagar{at}sergas.es

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Osteoarthritis (OA) has recently been defined as a ‘whole joint’ disease with pathological changes in all tissues, including articular cartilage degradation, subchondral bone thickening, osteophyte formation, synovial inflammation and degeneration of ligaments, and, in the knee, the menisci.1 OA is a chronic musculoskeletal disease that leads to pain and severe impairment of mobility. OA is the main cause of work incapacity and one of the most common reasons for visiting primary care physicians; its prevalence reaches up to 40% of people over the age of 70.2 In later stages of OA, patients experience limited mobility and persistent pain, often requiring reconstructive surgery at that time. Although OA is the most prevalent rheumatic disease, affecting 40 million patients in Europe, existing therapies are symptomatic and pursue only pain alleviation with no effect on slowing disease progression.3 ,4

While affecting all structures within a joint, OA has generally been defined as a disease characterised by loss of hyaline articular cartilage. Adult articular cartilage exists as four distinct cellular zones. The superficial zone consists of one to two layers of flattened chondrocytes expressing proteoglycan 4 or lubricin, SRY-box 9 (Sox9), type II collagen, aggrecan, tenascin C and low levels of cartilage intermediate layer protein. Chondrocytes of the intermediate zone are round in appearance, do not express lubricin, but do express higher levels of cartilage intermediate layer protein. The chondrocytes of the radial and calcified zones express markers of chondrocyte differentiation and hypertrophy, such as type X collagen and alkaline phosphatase. Each of the articular cartilage regions is normally maintained throughout adulthood unless stress-related injury, inflammation or a genetic defect leads to the loss of either the signals required to maintain these cells or the signals required to inhibit excessive differentiation of these cells. Disruption or impairment of the signals …

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