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An extra-erythrocyte role of haemoglobin body in chondrocyte hypoxia adaption

Although haemoglobin is a known carrier of oxygen in erythrocytes that functions to transport oxygen over a long range, its physiological roles outside erythrocytes are largely elusive1,2. Here we found that chondrocytes produced massive amounts of haemoglobin to form eosin-positive bodies in their cytoplasm. The haemoglobin body (Hedy) is a membraneless condensate characterized by phase separation. Production of haemoglobin in chondrocytes is controlled by hypoxia and is dependent on KLF1 rather than the HIF1/2α pathway. Deletion of haemoglobin in chondrocytes leads to Hedy loss along with severe hypoxia, enhanced glycolysis and extensive cell death in the centre of cartilaginous tissue, which is attributed to the loss of the Hedy-controlled oxygen supply under hypoxic conditions. These results demonstrate an extra-erythrocyte role of haemoglobin in chondrocytes, and uncover a heretofore unrecognized mechanism in which chondrocytes survive a hypoxic environment through Hedy. Haem ....

United States , Leica Biosystems , Perkin Elmer , Leica Microsystems , Sakura Finetechnical , Trizol Invitrogen , Agilent Bioanalyzer , Jena Bioscience , M Nacl Chinese Medicine Group Chemical Agent , Fourth Military Medical University , Autocuts Zhenjiang Lehua Technology , Camera Andor Technology , Bio Rad Image Lab , Department Of Pathology Xijing Hospital , Shanghai Biotechnology Corporation , Agilent Technologies , Sysmex Corporation , Shanghai Model Organisms Center , Genomics Institute , Proteome Discoverer Software , M Kcl Chinese Medicine Group Chemical Agent , Research Ethics Board Of The Xijing Hospital , Thermo Fisher , Cell Signaling Technology , Sigma Aldrich , Jackson Labs ,