TY - JOUR TI - Transcriptional regulation of cyclophilin D by BMP/Smad signaling and its role in osteogenic differentiation AU - Sautchuk, Rubens AU - Kalicharan, Brianna H AU - Escalera-Rivera, Katherine AU - Jonason, Jennifer H AU - Porter, George A AU - Awad, Hani A AU - Eliseev, Roman A A2 - Abu-Amer, Yousef A2 - Zaidi, Mone A2 - Avadhani, Narayan VL - 11 PY - 2022 DA - 2022/05/30 SP - e75023 C1 - eLife 2022;11:e75023 DO - 10.7554/eLife.75023 UR - https://doi.org/10.7554/eLife.75023 AB - Cyclophilin D (CypD) promotes opening of the mitochondrial permeability transition pore (MPTP) which plays a key role in both cell physiology and pathology. It is, therefore, beneficial for cells to tightly regulate CypD and MPTP but little is known about such regulation. We have reported before that CypD is downregulated and MPTP deactivated during differentiation in various tissues. Herein, we identify BMP/Smad signaling, a major driver of differentiation, as a transcriptional regulator of the CypD gene, Ppif. Using osteogenic induction of mesenchymal lineage cells as a BMP/Smad activation-dependent differentiation model, we show that CypD is in fact transcriptionally repressed during this process. The importance of such CypD downregulation is evidenced by the negative effect of CypD ‘rescue’ via gain-of-function on osteogenesis both in vitro and in a mouse model. In sum, we characterized BMP/Smad signaling as a regulator of CypD expression and elucidated the role of CypD downregulation during cell differentiation. KW - cyclophilin D KW - mitochondria KW - permeability transition KW - BMP/Smad KW - osteoprogenitor KW - bone JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -