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Eur J Pharmacol. 2017 Nov 15;815:202-209. doi: 10.1016/j.ejphar.2017.09.015. Epub 2017 Sep 15.

Macrolactin F inhibits RANKL-mediated osteoclastogenesis by suppressing Akt, MAPK and NFATc1 pathways and promotes osteoblastogenesis through a BMP-2/smad/Akt/Runx2 signaling pathway.

Author information

1
Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeonju 561-756, Republic of Korea.
2
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
3
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: h5choi@yu.ac.kr.
4
Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: ysoh@jbnu.ac.kr.

Abstract

The balance between bone formation and bone resorption is maintained by osteoblasts and osteoclasts. In the current study, macrolactin F (MF) was investigated for novel biological activity on the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages (BMMs). We found that RANKL-induced osteoclast formation and differentiation from BMMs was significantly inhibited by MF in a dose-dependent manner without cytotoxicity. RANKL-induced F-actin ring formation and bone resorption activity in BMMs which was attenuated by MF. In addition, MF suppressed the expression of osteoclast-related genes, including c-myc, RANK, tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T cells c1 (NFATc1), cathepsin K and matrix metalloproteinase 9 (MMP9). Furthermore, the protein expression NFATc1, c-Fos, MMP9, cathepsin K and phosphorylation of Jun N-terminal kinase (JNK), p38 and Akt were also down-regulated by MF treatment. Interestingly, MF promoted pre-osteoblast cell differentiation on Alizarin Red-mineralization activity, alkaline phosphatase (ALP) activity, and the expression of osteoblastogenic markers including Runx2, Osterix, Smad4, ALP, type I collagen alpha 1 (Col1α), osteopontin (OPN), and osteocalcin (OCN) via activation of the BMP-2/smad/Akt/Runx2 pathway on MC3T3-E1. Taken together, these results indicate that MF may be useful as a therapeutic agent to enhance bone health and treat osteoporosis.

KEYWORDS:

Macrolactin F; Osteoblast; Osteoclast; Osteoporosis; RANKL

PMID:
28919027
DOI:
10.1016/j.ejphar.2017.09.015
[Indexed for MEDLINE]

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