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  • Title: Abnormal thyroid hormone receptor signaling in osteoarthritic osteoblasts regulates microangiogenesis in subchondral bone.
    Author: Li L, Li M, Pang Y, Wang J, Wan Y, Zhu C, Yin Z.
    Journal: Life Sci; 2019 Dec 15; 239():116975. PubMed ID: 31654748.
    Abstract:
    AIMS: Previous 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 METHODS: THRs 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 FINDINGS: THRs 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 mainly regulated VEGF expression. Intra-articular injection with THRα siRNA reduced angiogenic activities in OA model mice subchondral bone and ameliorated cartilage degradation. Micro-CT analysis displayed that the aberrant subchondral bone formation in OA was promoted. SIGNIFICANCE: The microangiogenesis in subchondral bone may be partly attributed to abnormal THRα signaling in osteoblasts, and local inhibition of the THRα could be a potential target to treat OA.
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