Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7

Abstract Cell surface heparan sulfate proteoglycan (HSPG)-mediated endocytosis results in poor yields of recombinant human bone morphogenetic proteins (rhBMPs) from CHO cell cultures. Upon incubation of rhBMP-2 and rhBMP-7 with CHO cells at 37 °C, both rhBMP-2 and rhBMP-7 bound to the cell surface H...

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Autores principales:	Mi Gyeom Kim, Che Lin Kim, Young Sik Kim, Ju Woong Jang, Gyun Min Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a7f876b8bcde4ab1807b9a3c638cb120
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spelling	oai:doaj.org-article:a7f876b8bcde4ab1807b9a3c638cb1202021-12-02T13:30:09ZSelective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-710.1038/s41598-021-82955-12045-2322https://doaj.org/article/a7f876b8bcde4ab1807b9a3c638cb1202021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82955-1https://doaj.org/toc/2045-2322Abstract Cell surface heparan sulfate proteoglycan (HSPG)-mediated endocytosis results in poor yields of recombinant human bone morphogenetic proteins (rhBMPs) from CHO cell cultures. Upon incubation of rhBMP-2 and rhBMP-7 with CHO cells at 37 °C, both rhBMP-2 and rhBMP-7 bound to the cell surface HSPGs in CHO cells, but only rhBMP-2 was actively internalized into CHO cells. Cell surface HSPGs were found to serve as the main receptor for rhBMP-2 internalization. It was also found that the cell surface HSPG-mediated endocytosis of rhBMP-2 occurred through both the clathrin- and caveolin-dependent pathways. Blockage of rhBMP-2 internalization by the addition of structural analogs of HSPGs such as dextran sulfate (DS) and heparin dramatically increased rhBMP-2 production in recombinant CHO (rCHO) cell cultures. Compared to the control cultures, addition of DS (1.0 g/L) and heparin (0.2 g/L) resulted in a 22.0- and 19.0-fold increase in the maximum rhBMP-2 concentration, respectively. In contrast, the production of rhBMP-7, which was not internalized into the rCHO cells, did not dramatically increase upon addition of DS and heparin. Taken together, rhBMPs have a different fate in terms of HSPG-mediated internalization in CHO cells. HSPG-mediated endocytosis of each rhBMP should be understood individually to increase the rhBMP yield in rCHO cell cultures.Mi Gyeom KimChe Lin KimYoung Sik KimJu Woong JangGyun Min LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mi Gyeom Kim Che Lin Kim Young Sik Kim Ju Woong Jang Gyun Min Lee Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7
description	Abstract Cell surface heparan sulfate proteoglycan (HSPG)-mediated endocytosis results in poor yields of recombinant human bone morphogenetic proteins (rhBMPs) from CHO cell cultures. Upon incubation of rhBMP-2 and rhBMP-7 with CHO cells at 37 °C, both rhBMP-2 and rhBMP-7 bound to the cell surface HSPGs in CHO cells, but only rhBMP-2 was actively internalized into CHO cells. Cell surface HSPGs were found to serve as the main receptor for rhBMP-2 internalization. It was also found that the cell surface HSPG-mediated endocytosis of rhBMP-2 occurred through both the clathrin- and caveolin-dependent pathways. Blockage of rhBMP-2 internalization by the addition of structural analogs of HSPGs such as dextran sulfate (DS) and heparin dramatically increased rhBMP-2 production in recombinant CHO (rCHO) cell cultures. Compared to the control cultures, addition of DS (1.0 g/L) and heparin (0.2 g/L) resulted in a 22.0- and 19.0-fold increase in the maximum rhBMP-2 concentration, respectively. In contrast, the production of rhBMP-7, which was not internalized into the rCHO cells, did not dramatically increase upon addition of DS and heparin. Taken together, rhBMPs have a different fate in terms of HSPG-mediated internalization in CHO cells. HSPG-mediated endocytosis of each rhBMP should be understood individually to increase the rhBMP yield in rCHO cell cultures.
format	article
author	Mi Gyeom Kim Che Lin Kim Young Sik Kim Ju Woong Jang Gyun Min Lee
author_facet	Mi Gyeom Kim Che Lin Kim Young Sik Kim Ju Woong Jang Gyun Min Lee
author_sort	Mi Gyeom Kim
title	Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7
title_short	Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7
title_full	Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7
title_fullStr	Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7
title_full_unstemmed	Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7
title_sort	selective endocytosis of recombinant human bmps through cell surface heparan sulfate proteoglycans in cho cells: bmp-2 and bmp-7
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a7f876b8bcde4ab1807b9a3c638cb120
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Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7

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