K-carrageenan stimulates pre-osteoblast proliferation and osteogenic differentiation: A potential factor for the promotion of bone regeneration?

Wei Cao, Jianfeng Jin, Gang Wu, Nathalie Bravenboer, Marco N. Helder, Janak L. Pathak, Behrouz Zandieh-Doulabi, Jolanda M.A. Hogervorst, Shingo Matsukawa, Lester C. Geonzon, Rommel G. Bacabac, Engelbert A.J.M. Schulten, Jenneke Klein-Nulend*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Current cell-based bone tissue regeneration strategies cannot cover large bone defects. K-carrageenan is a highly hydrophilic and biocompatible seaweed-derived sulfated polysaccharide, that has been proposed as a promising candidate for tissue engineering applications. Whether κ-carrageenan can be used to enhance bone regeneration is still unclear. In this study, we aimed to investigate whether κ-carrageenan has osteogenic potential by testing its effect on pre-osteoblast proliferation and osteogenic differentiation in vitro. Treatment with κ-carrageenan (0.5 and 2 mg/mL) increased both MC3T3-E1 pre-osteoblast adhesion and spreading at 1 h. K-carrageenan (0.125–2 mg/mL) dose-dependently increased pre-osteoblast proliferation and metabolic activity, with a maximum effect at 2 mg/mL at day three. K-carrageenan (0.5 and 2 mg/mL) increased osteogenic differentiation, as shown by enhanced alkaline phosphatase activity (1.8-fold increase at 2 mg/mL) at day four, and matrix mineralization (6.2-fold increase at 2 mg/mL) at day 21. K-carrageenan enhanced osteogenic gene expression (Opn, Dmp1, and Mepe) at day 14 and 21. In conclusion, κ-carrageenan promoted MC3T3-E1 pre-osteoblast adhesion and spreading, metabolic activity, proliferation, and osteogenic differentiation, suggesting that κ-carrageenan is a potential osteogenic inductive factor for clinical application to enhance bone regeneration.

Original languageEnglish
Article number6131
Issue number20
Publication statusPublished - 2 Oct 2021

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