Effectiveness and mode of action of a combination therapy for heterotopic ossification with a retinoid agonist and an anti-inflammatory agent

Bone
Sayantani SinhaMasahiro Iwamoto

Abstract

Heterotopic ossification (HO) consists of ectopic cartilage and bone formation following severe trauma or invasive surgeries, and a genetic form of it characterizes patients with Fibrodysplasia Ossificans Progressiva (FOP). Recent mouse studies showed that HO was significantly inhibited by systemic treatment with a corticosteroid or the retinoic acid receptor γ agonist Palovarotene. Because these drugs act differently, the data raised intriguing questions including whether the drugs affected HO via similar means, whether a combination therapy would be more effective or whether the drugs may hamper each other's action. To tackle these questions, we used an effective HO mouse model involving subcutaneous implantation of Matrigel plus rhBMP2, and compared the effectiveness of prednisone, dexamathaosone, Palovarotene or combination of. Each corticosteroid and Palovarotene reduced bone formation at max doses, and a combination therapy elicited similar outcomes without obvious interference. While Palovarotene had effectively prevented the initial cartilaginous phase of HO, the steroids appeared to act more on the bony phase. In reporter assays, dexamethasone and Palovarotene induced transcriptional activity of their respective GRE or...Continue Reading

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Citations

Nov 10, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Toshihiro InubushiYu Yamaguchi
Aug 2, 2017·The Journal of Clinical Investigation·Kyosuke HinoMakoto Ikeya
Mar 29, 2018·International Journal of Molecular Sciences·Serena CappatoRenata Bocciardi
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Jul 3, 2017·Translational Research : the Journal of Laboratory and Clinical Medicine·Devaveena DeyThomas A Davis
Aug 23, 2021·Biochemical and Biophysical Research Communications·Yangyang Hu, Zhe Wang
Nov 18, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Mingming YanMuhammad Farooq Rai

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