Refereed journal article or data article (A1)

Signaling pathways in human osteoclasts differentiation: ERK1/2 as a key player




List of AuthorsPennanen Paula, Kallionpää Roope A, Peltonen Sirkku, Nissinen Liisa, Kähäri Veli-Matti, Heervä Eetu, Peltonen Juha

PublisherSpringer

Publication year2021

JournalMolecular Biology Reports

Journal acronymMol Biol Rep

Volume number48

Start page1243

End page1254

eISSN1573-4978

DOIhttp://dx.doi.org/10.1007/s11033-020-06128-5

URLhttps://link.springer.com/article/10.1007/s11033-020-06128-5

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/50887247


Abstract

Little is known about the signaling pathways involved in the differentiation of human osteoclasts. The present study evaluated the roles of the Ras/PI3K/Akt/mTOR, Ras/Raf/MEK1/2/ERK1/2, calcium-PKC, and p38 signaling pathways in human osteoclast differentiation. Mononuclear cells were isolated from the peripheral blood of control persons and patients with neurofibromatosis 1 (NF1), and the cells were differentiated into osteoclasts in the presence of signaling pathway inhibitors. Osteoclast differentiation was assessed using tartrate-resistant acid phosphatase 5B. Inhibition of most signaling pathways with chemical inhibitors decreased the number of human osteoclasts and disrupted F-actin ring formation, while the inhibition of p38 resulted in an increased number of osteoclasts, which is a finding contradictory to previous murine studies. However, the p38 inhibition did not increase the bone resorption capacity of the cells. Ras-inhibitor FTS increased osteoclastogenesis in samples from control persons, but an inhibitory effect was observed in NF1 samples. Inhibition of MEK, PI3K, and mTOR reduced markedly the number of NF1-deficient osteoclasts, but no effect was observed in control samples. Western blot analyses showed that the changes in the phosphorylation of ERK1/2 correlated with the number of osteoclasts. Our results highlight the fact that osteoclastogenesis is regulated by multiple interacting signaling pathways and emphasize that murine and human findings related to osteoclastogenesis are not necessarily equivalent.


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Last updated on 2022-19-12 at 15:48