LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

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

Photo from wikipedia

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… Click to show full abstract

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‐&kgr;B (NF‐&kgr;B) 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 (Col1&agr;), 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: akt; akt runx2; bmp smad; bone; smad akt; activity

Journal Title: European Journal of Pharmacology
Year Published: 2017

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.