Effect of Ishophloroglucin A Isolated from Ishige okamurae on In Vitro Osteoclastogenesis and Osteoblastogenesis

Author:

Cho Su-Hyeon12,Kim Hyun-Soo3,Jung Hye-Yeon4,Park Jae-Il4ORCID,Jang You-Jee5ORCID,Ahn Juhee2ORCID,Kim Kil-Nam16ORCID

Affiliation:

1. Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon 24341, Republic of Korea

2. Department of Medical Biomaterials Engineering, College of Biomedical Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea

3. National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea

4. Gwangju Center, Korea Basic Science Institute (KBSI), Gwangju 61751, Republic of Korea

5. Department of Biomedical Laboratory Science, Honam University, Gwangju 62399, Republic of Korea

6. Department of Bio-Analysis Science, University of Science & Technology, Daejeon 34113, Republic of Korea

Abstract

The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is essential for the bone remodeling process. This study aimed to investigate the effect of Ishophloroglucin A (IPA) isolated from Ishige okamurae on the function of osteoclasts and osteoblasts in vitro. First, we demonstrated the effect of IPA on osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW 264.7 cells. IPA inhibited the tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation in RANKL-induced RAW 264.7 cells. Moreover, it inhibited the RANKL-induced osteoclast-related factors, such as TRAP, matrix metalloproteinase-9 (MMP-9), and calcitonin receptor (CTR), and transcription factors, such as nuclear factor of activated T cells 1 (NFATc1) and c-Fos. IPA significantly suppressed RANKL-activated extracellular signal-regulated kinase (ERK), and NF-κB in RAW 264.7 cells. Our data indicated that the ERK and NF-κB pathways were associated with the osteoclastogenesis inhibitory activity of IPA. Next, we demonstrated the effect of IPA on osteoblastogenesis in MG-63 cells. IPA significantly promoted alkaline phosphatase (ALP) activity in MG-63 cells, along with the osteoblast differentiation-related markers bone morphogenetic protein 2 (BMP2), type 1 collage (COL1), p-Smad1/5/8, and Runx2, by activating the MAPK signaling pathways. Taken together, the study indicated that IPA could be effective in treating bone diseases, such as osteoporosis.

Funder

National Research Foundation of Korea

Publisher

MDPI AG

Subject

Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science

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