TY - JOUR TI - Differences in pathways contributing to thyroid hormone effects on postnatal cartilage calcification versus secondary ossification center development AU - Gomez, Gustavo A AU - Aghajanian, Patrick AU - Pourteymoor, Sheila AU - Larkin, Destiney AU - Mohan, Subburaman A2 - Zaidi, Mone A2 - Iqbal, Jameel A2 - Latif, Rauf VL - 11 PY - 2022 DA - 2022/01/31 SP - e76730 C1 - eLife 2022;11:e76730 DO - 10.7554/eLife.76730 UR - https://doi.org/10.7554/eLife.76730 AB - The proximal and distal femur epiphyses of mice are both weight-bearing structures derived from chondrocytes but differ in development. Mineralization at the distal epiphysis occurs in an osteoblast-rich secondary ossification center (SOC), while the chondrocytes of the proximal femur head (FH), in particular, are directly mineralized. Thyroid hormone (TH) plays important roles in distal knee SOC formation, but whether TH also affects proximal FH development remains unexplored. Here, we found that TH controls chondrocyte maturation and mineralization at the FH in vivo through studies in thyroid stimulating hormone receptor (Tshr-/-) hypothyroid mice by X-ray, histology, transcriptional profiling, and immunofluorescence staining. Both in vivo and in vitro studies conducted in ATDC5 chondrocyte progenitors concur that TH regulates expression of genes that modulate mineralization (Ibsp, Bglap2, Dmp1, Spp1, and Alpl). Our work also delineates differences in prominent transcription factor regulation of genes involved in the different mechanisms leading to proximal FH cartilage calcification and endochondral ossification at the distal femur. The information on the molecular pathways contributing to postnatal cartilage calcification can provide insights on therapeutic strategies to treat pathological calcification that occurs in soft tissues such as aorta, kidney, and articular cartilage. KW - thyroid hormone KW - endochondral bone formation KW - cartilage calcification KW - femoral head KW - chondrocytes KW - osteoblasts JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -