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

doi:10.3390/molecules26206131

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 Journal › Article › Academic › peer-review

Abstract

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 language	English
Article number	6131
Pages (from-to)	1-16
Number of pages	16
Journal	Molecules
Volume	26
Issue number	20
DOIs	https://doi.org/10.3390/molecules26206131
Publication status	Published - 2 Oct 2021

Bibliographical note

Special Issue: Advances in Biomaterials for Drug Delivery and Tissue Regeneration.

Funding Information:
Funding: This work was granted by the China Scholarship Council (CSC, no. 201808440487 (W. Cao) and no. 201608530156 (J. Jin)). This work was also granted by Health-Holland (project no. LSHM19016, “BB”). L.C. Geonzon received financial support of JSPS KAKENHI grant no.20F20388. R.G. Bacabac was funded by DOST-PCIEERD project no. 09438, and received logistic support from the USC Research Office and Department of Physics.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Funding

Funding: This work was granted by the China Scholarship Council (CSC, no. 201808440487 (W. Cao) and no. 201608530156 (J. Jin)). This work was also granted by Health-Holland (project no. LSHM19016, “BB”). L.C. Geonzon received financial support of JSPS KAKENHI grant no.20F20388. R.G. Bacabac was funded by DOST-PCIEERD project no. 09438, and received logistic support from the USC Research Office and Department of Physics.

Funders	Funder number
Department of Physics
USC Research Office
Health~Holland	LSHM19016
Health~Holland
Japan Society for the Promotion of Science	20F20388
Japan Society for the Promotion of Science
China Scholarship Council	201608530156, 201808440487
China Scholarship Council
Philippine Council for Industry, Energy, and Emerging Technology Research and Development	09438
Philippine Council for Industry, Energy, and Emerging Technology Research and Development

Keywords

Bone defect
Bone regeneration
Cell proliferation
Cell-based bone tissue engineering
MC3T3-E1 pre-osteoblast
Osteogenic differentiation
κ-carrageenan

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules26206131

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Cao, W., Jin, J., Wu, G., Bravenboer, N., Helder, M. N., Pathak, J. L., Zandieh-Doulabi, B., Hogervorst, J. M. A., Matsukawa, S., Geonzon, L. C., Bacabac, R. G., Schulten, E. A. J. M., & Klein-Nulend, J. (2021). K-carrageenan stimulates pre-osteoblast proliferation and osteogenic differentiation: A potential factor for the promotion of bone regeneration? Molecules, 26(20), 1-16. Article 6131. https://doi.org/10.3390/molecules26206131

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

abstract = "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.",

keywords = "Bone defect, Bone regeneration, Cell proliferation, Cell-based bone tissue engineering, MC3T3-E1 pre-osteoblast, Osteogenic differentiation, κ-carrageenan",

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

note = "Special Issue: Advances in Biomaterials for Drug Delivery and Tissue Regeneration. Funding Information: Funding: This work was granted by the China Scholarship Council (CSC, no. 201808440487 (W. Cao) and no. 201608530156 (J. Jin)). This work was also granted by Health-Holland (project no. LSHM19016, “BB”). L.C. Geonzon received financial support of JSPS KAKENHI grant no.20F20388. R.G. Bacabac was funded by DOST-PCIEERD project no. 09438, and received logistic support from the USC Research Office and Department of Physics. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = oct,

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doi = "10.3390/molecules26206131",

language = "English",

volume = "26",

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Cao, W, Jin, J , Wu, G, Bravenboer, N, Helder, MN, Pathak, JL, Zandieh-Doulabi, B , Hogervorst, JMA, Matsukawa, S, Geonzon, LC, Bacabac, RG, Schulten, EAJM & Klein-Nulend, J 2021, 'K-carrageenan stimulates pre-osteoblast proliferation and osteogenic differentiation: A potential factor for the promotion of bone regeneration?', Molecules, vol. 26, no. 20, 6131, pp. 1-16. https://doi.org/10.3390/molecules26206131

TY - JOUR

T1 - K-carrageenan stimulates pre-osteoblast proliferation and osteogenic differentiation

T2 - A potential factor for the promotion of bone regeneration?

AU - Cao, Wei

AU - Jin, Jianfeng

AU - Wu, Gang

AU - Bravenboer, Nathalie

AU - Helder, Marco N.

AU - Pathak, Janak L.

AU - Zandieh-Doulabi, Behrouz

AU - Hogervorst, Jolanda M.A.

AU - Matsukawa, Shingo

AU - Geonzon, Lester C.

AU - Bacabac, Rommel G.

AU - Schulten, Engelbert A.J.M.

AU - Klein-Nulend, Jenneke

N1 - Special Issue: Advances in Biomaterials for Drug Delivery and Tissue Regeneration. Funding Information: Funding: This work was granted by the China Scholarship Council (CSC, no. 201808440487 (W. Cao) and no. 201608530156 (J. Jin)). This work was also granted by Health-Holland (project no. LSHM19016, “BB”). L.C. Geonzon received financial support of JSPS KAKENHI grant no.20F20388. R.G. Bacabac was funded by DOST-PCIEERD project no. 09438, and received logistic support from the USC Research Office and Department of Physics. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/10/2

Y1 - 2021/10/2

N2 - 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.

AB - 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.

KW - Bone defect

KW - Bone regeneration

KW - Cell proliferation

KW - Cell-based bone tissue engineering

KW - MC3T3-E1 pre-osteoblast

KW - Osteogenic differentiation

KW - κ-carrageenan

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DO - 10.3390/molecules26206131

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C2 - 34684714

AN - SCOPUS:85117182117

SN - 1420-3049

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JO - Molecules

JF - Molecules

IS - 20

M1 - 6131

ER -

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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