Abnormal thyroid hormone receptor signaling in osteoarthritic osteoblasts regulates microangiogenesis in subchondral bone

Publication date: Available online 22 October 2019Source: Life SciencesAuthor(s): Li Lei, Meng Li, Yiqun Pang, Jun Wang, Yunpeng Wan, Chen Zhu, Yin ZongshengAbstractAimsPrevious study indicated that the increase of local bio-availability of 3′3′5-triiodothyronine (T3) influenced osteoarthritis (OA) initiation. We aimed to investigate the role of thyroid hormone receptors (THRs) signaling in OA osteoblasts.Materials and methodsTHRs expression in OA was detected by immunohistochemistry, immunofluorescence, RT-qPCR and western blotting. These effects on the expression of angiogenesis-related factors were examined after THRα or THRβ knockdown in OA osteoblasts. Fluorescence in situ hybridization was used to confirm the leading receptor for regulating angiogenesis-related factors. Co-culture model was utilized to observe the MMPs expression in chondrocytes after THRα knockdown in osteoblasts. The in vivo effects were also studied after intra-articular injection with THRα siRNA in OA model mice. Micro-CT and immunohistochemistry were employed to evaluate the changes of subchondral bone.Key findingsTHRs expression and nuclear translocation were upregulated in human OA osteoblasts. Immunohistochemistry showed that angiogenic activities were increased in OA subchondral bone of human and mice. VEGF, HIF-1α and IGF-1, these THR downstream genes were downregulated after THRα knockdown in OA osteoblasts. Fluorescence in situ hybridization further indicated that THRα signaling m...
Source: Life Sciences - Category: Biology Source Type: research