ArticleScientific reports2021
Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Priming Cells with Modulators of Cellular Signaling Ensures Enhanced Selectivity of HSPG-Specific Protein-Drug Conjugate Delivery.Journal of the American Chemical Society · 2026Article
- Xylt2 Knockout Eliminates O-Xylosylation and Enhances Bone Morphogenetic Protein 2 Production in Chinese Hamster Ovary Cells.Biotechnology journal · 2026Article
- A new mRNA structure prediction based approach to identifying improved signal peptides for bone morphogenetic protein 2.BMC biotechnology · 2024Article
- Targeting heparan sulfate-protein interactions with oligosaccharides and monoclonal antibodies.Frontiers in molecular biosciences · 2023Review
- Expression of heterologous heparan sulphate binding protein of3 Biotech · 2023Article
- Could BMPs Therapy Be Improved if BMPs Were Used in Composition Acting during Bone Formation in Endochondral Ossification?International journal of molecular sciences · 2022Review
- Cell trafficking and regulation of osteoblastogenesis by extracellular vesicle associated bone morphogenetic protein 2.Journal of extracellular vesicles · 2021Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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