Insight into the function of DIO2, a susceptibility gene in human osteoarthritis, as an inducer of cartilage damage in a rat model: is there a role for chondrocyte hypertrophy?

Adult Mice Lacking the Type 2 Iodothyronine Deiodinase Have Increased Subchondral Bone but Normal Articular Cartilage

“…This is a complex question because OA may result from primary abnormalities in articular chondrocytes, changes in adjacent subchondral bone that lead to secondary cartilage damage and degeneration, or from defects in both tissues. Although it is well established that both subchondral bone remodeling and articular cartilage damage occur in OA, it is not clear whether these alterations occur simultaneously or whether subchondral bone changes result in cartilage damage or vice versa (3,9,40,41). For example, cathepsin K knockout mice have increased subchondral bone mineralization and are protected from OA (42), whereas rabbits treated with parathyroid hormone have increased subchondral bone mineral density but worsened articular cartilage integrity (43).…”

“…Recent data suggest that altered thyroid hormone availability in articular cartilage or joint tissues may play a key role in predisposition to OA (5)(6)(7)(8)(9). Normal euthyroid status is maintained by the hypothalamic-pituitary-thyroid axis via a negative feedback loop in which thyroid hormones produced by the thyroid gland inhibit synthesis and secretion of thyrotropin (TSH) from the anterior pituitary.…”

Chondrocyte hypertrophy in skeletal development, growth, and disease

“…Another intriguing gene is DIO2 , encoding an enzyme involved in the activation of thyroid hormone (Meulenbelt et al, ). Because thyroid hormone promotes chondrocyte hypertrophy (Ballock and O'Keefe, ), a connection between SNPs in the DIO2 gene, altered chondrocyte hypertrophy, and OA risk appears likely (Goldring, ). However, like many of the molecular events described in this review, this model still needs experimental validation, in particular in vivo .…”

Cartilage Tissue Engineering: Recent Advances and Perspectives from Gene Regulation/Therapy

“…Since autologous chondrocytes are often isolated from patients with OA, the suitability of OA chondrocytes for cartilage engineering is examined . However, autologous OA chondrocytes appear less appropriate for articular cartilage repair . Alternatively, allogeneic, cryopreserved chondrocytes may provide another source of chondrocytes for cartilage regeneration …”