Endocrine Abstracts

Local regulation of T₃ action in bone and cartilage is a novel mechanism underlying the pathogenesis of osteoarthritis (OA). Accelerated chondrocyte differentiation is a hallmark of OA and T₃ regulates this process. The type 1 and 2 deiodinases (D1, D2) convert the pro-hormone T₄ to the active hormone T₃ whilst D3 inactivates both T₃ and T₄. D1 contributes to circulating T₃ levels and local T₃ availability is determined by the relative activities of D2 and D3 in target cells. Population studies have recently identified DIO2 and DIO3 as OA susceptibility loci, whilst phase three trials of the T₃ analogue Eprotirome were terminated after toxicology studies revealed cartilage destruction. Thus, increased T₃ action in chondrocytes may increase susceptibility to OA. We hypothesised that deletion of the T₄ activating enzymes would confer protection against OA and thus studied knee joints obtained from 16-week-old adult D2KO and D1D2KO mice 5 μm coronal and sagittal sections at 80 μm intervals were stained with Safranin-O Fast-Green and scored according to the Osteoarthritis Research Society International (OARSI) grading scale (0= normal articular cartilage and 6= clefts or erosions extending to the mineralizing front and covering >75% of the articular cartilage). Maximum and standardized OA scores were determined. A maximum score of two was recorded in D2KO, D1D2KO and WT mice (Kruskal–Wallis, NS, n=3–5), indicating loss of articular cartilage surface lamina and the presence of superficial clefts. Standardized OA scores also did not differ among genotypes (WT 7.84 (0–13.5); D2KO 2.07 (0–12.8); D1D2KO 8.26 (0–15.2); median (range) total osteoarthritis score/articular surface, Kruskal–Wallis, ns, n=3–5).

These data demonstrate that deletion of thyroid hormone activating enzymes does not affect the onset of spontaneous OA and that disease provocation models will be required to determine the role of local T₃ availability in OA pathogenesis.

Declaration of funding: This work was supported by an ARUK Clinical Research Fellowship to J A W (grant number 19744).