Lin Yuan-Yu, Takemoto Jon Y, Chang Cheng-Wei T, Peng Ching-An
Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan.
Department of Biology, Utah State University, Logan, UT, United States.
Biochem Biophys Res Commun. 2022 Sep 3;619:56-61. doi: 10.1016/j.bbrc.2022.06.042. Epub 2022 Jun 15.
Heme oxygenase-1 (HO-1) expression promotes osteogenesis, but the mechanisms remain unclear and therapeutic strategies using it to target bone disorders such as osteoporosis have not progressed. Mesobiliverdin IXα is a naturally occurring bilin analog of HO-1 catalytic product biliverdin IXα. Inclusion of mesobiliverdin IXα in the feed diet of ovariectomized osteoporotic mice was observed to increase femur bone volume, trabecular thickness and osteogenesis serum markers osteoprotegrin and osteocalcin and to decrease bone resorption serum markers cross-linked N-teleopeptide and tartrate-resistant acid phosphatase 5b. Moreover, in vitro exposure of human bone marrow mesenchymal stem cells to mesobiliverdin IXα enhanced osteogenic differentiation efficiency by two-fold over non-exposed controls. Our results imply that mesobiliverdin IXα promotes osteogenesis in ways that reflect the potential therapeutic effects of induced HO-1 expression in alleviating osteoporosis.
血红素加氧酶-1（HO-1）的表达可促进骨生成，但其机制仍不清楚，并且利用该酶治疗诸如骨质疏松症等骨骼疾病的策略尚未取得进展。中胆绿素IXα是HO-1催化产物胆绿素IXα的天然存在的二吡咯化合物类似物。研究发现，在去卵巢骨质疏松小鼠的饲料中添加中胆绿素IXα，可增加股骨骨体积、小梁厚度以及成骨血清标志物骨保护素和骨钙素，并降低骨吸收血清标志物交联N-端肽和抗酒石酸酸性磷酸酶5b。此外，体外将人骨髓间充质干细胞暴露于中胆绿素IXα，可使其成骨分化效率比未暴露的对照提高两倍。我们的研究结果表明，中胆绿素IXα促进骨生成的方式反映了诱导HO-1表达在缓解骨质疏松症方面的潜在治疗作用。
