Fig. 4.

Proposed model for thyroid hormone-mediated early post-natal development of the secondary ossification center (SOC). During embryonic and early post-natal development when thyroid hormone (TH) levels are low, epiphyseal chondrocytes express elevated levels of SHH, which acts through GLI1 to maintain these cells in proliferative immature state by activating Sox5/6/9 transcriptional activity. At P6/P7, rise in TH increases TRβ1expression and thereby IHH expression. IHH acts through GLI2 to decrease SOX9 and COL2 expression, while MMP13 and ADAMTS5 expression increases to deplete the COL2 matrix. Pre-hypertrophic chondrocyte (CC)s begin to express COL10 and OSX in the P8/P9 period. These in turn activate DMP1 and ALP in the SOC, meanwhile blood vessels invade from the periphery of the articular CCs. Text and image obtained from ref. ⁴