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

Abstract

Although adult D2KO mice have normal articular cartilage and no other features of spontaneous joint damage, they exhibit increased subchondral bone mineral content.

New insights into thyroid hormone action

“…The SNP rs225014 upstream of D2 has been associated with risk of osteoarthritis and carriers of this allele show defective epigenetic silencing of D2 in chondrocytes (Bomer et al, 2015). In contrast, D2 ablation in mice induced increased mineral content in bones with a normal cartilage phenotype (Waung, Bassett, & Williams, 2015). Further work will be required to delineate the role of deiodinases and T3 production in osteoarthritis.…”

Hypothyroidism Increases 90-Day Complications and Costs Following Primary Total Knee Arthroplasty

“…Thyroid hormone has a number of systemic and musculoskeletal functions including bone remodeling and maintaining articular cartilage health [27,28]. Research suggests an increased risk of osteoarthritis among people with thyroid disease [29,30]. The reported prevalence of hypothyroidism in the total joints population is up to 18%, which is significantly higher than in the general population [31].…”

Novel Insights into Osteoarthritis Joint Pathology from Studies in Mice

“…They reported increased mineral content in subchondral bone in Dio2 KO mice at 16 weeks of age with no change in cartilage structure [65]. Based on evidence of the chondroprotective effect of Dio2 deletion on exercise-induced OA, as described above [64••], it would be interesting to see a follow-up study on spontaneous OA development during aging in Dio2-deficient mice, as the augmented subchondral mineralization would probably promote early OA.…”

“…However, the global deletion of Dio2 protects mice from exercise-induced cartilage breakdown and associated synovitis. Although Dio2 catalyzes the conversion of thyroxine to active thyroid hormone in skeletal tissues, the tissuespecific consequences of this are not clear, as more recent evidence suggests that Dio2 has important roles in bone, but not cartilage homeostasis [65]. These effects will be further discussed in the next section.…”

“…Waung et al [65] reported recently on the isolated effects of Dio2 deletion on the mineralization of subchondral bone. They reported increased mineral content in subchondral bone in Dio2 KO mice at 16 weeks of age with no change in cartilage structure [65].…”