Targeting anti-chondrogenic factors for the stimulation of chondrogenesis: A new paradigm in cartilage repair

Trauma and age-related cartilage disorders represent a major global cause of morbidity, resulting in chronic pain and disability in patients. A lack of effective therapies, together with a rapidly aging population, creates an impressive clinical and economic burden on healthcare systems. In this scenario, experimental therapies based on transplantation or in situ stimulation of skeletal Mesenchymal Stem/progenitor Cells (MSCs) have raised great interest for cartilage repair. Nevertheless, the challenge of guiding MSC differentiation and preventing cartilage hypertrophy and calcification still needs to be overcome. While research has mostly focused on the stimulation of cartilage anabolism using growth factors, several issues remain unresolved prompting the field to search for novel solutions. Recently, inhibition of anti-chondrogenic regulators has emerged as an intriguing opportunity. Anti-chondrogenic regulators include extracellular proteins as well as intracellular transcription factors and microRNAs that act as potent inhibitors of pro-chondrogenic signals. Suppression of these inhibitors can enhance MSC chondrogenesis and production of cartilage matrix. We here review the current knowledge concerning different types of anti-chondrogenic regulators. We aim to highlight novel therapeutic targets for cartilage repair and discuss suitable tools for suppressing their anti-chondrogenic functions. Further effort is needed to unveil the therapeutic perspectives of this approach and pave the way for effective treatment of cartilage injuries in patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.