Epiphyseal Chondrocyte Secondary Ossification Centers Require Thyroid Hormone Activation of Indian Hedgehog and Osterix Signaling

摘要: Thyroid hormones (THs) are known to regulate endochondral ossification during skeletal development via acting directly in chondrocytes and osteoblasts. In this study, we focused on TH effects the secondary center (SOC) because time of appearance SOCs several species coincides with when peak levels attained. Accordingly, micro-computed tomography (µCT) evaluation femurs tibias at day 21 TH-deficient control mice revealed that is severely compromised owing deficiency treatment for 10 days completely rescued phenotype. Staining cartilage bone epiphysis whereas all converted into prepubertal mice, conversion failed occur mice. Immunohistochemistry studies thyroid stimulating hormone receptor mutant (Tshr(-/-) ) induced expression Indian hedgehog (Ihh) Osx type 2 collagen (Col2)-expressing SOC 7, which subsequently differentiate (Col10)/osteocalcin-expressing chondro/osteoblasts 10. Consistent these data, tibia cultures from 3-day-old ng/mL increased Osx, Col10, alkaline phosphatase (ALP), osteocalcin by sixfold 60-fold. Furthermore, knockdown TH-induced increase using lentiviral small hairpin RNA (shRNA) significantly blocked ALP chondrocytes. Treatment chondrogenic cells an Ihh inhibitor abolished chondro/osteoblast differentiation formation. Our findings indicate regulates initiation progression differentiating matrix-producing osteoblasts