c-Src and IL-6 inhibit osteoblast differentiation and integrate IGFBP5 signalling

Barbara Peruzzi, Alfredo Cappariello, Andrea Del Fattore, Nadia Rucci, Fabrizio De Benedetti and Anna Teti ()
Additional contact information
Barbara Peruzzi: University of L'Aquila, Via Vetoio – Coppito 2
Alfredo Cappariello: Ospedale Pediatrico Bambino Gesù
Andrea Del Fattore: University of L'Aquila, Via Vetoio – Coppito 2
Nadia Rucci: University of L'Aquila, Via Vetoio – Coppito 2
Fabrizio De Benedetti: Ospedale Pediatrico Bambino Gesù
Anna Teti: University of L'Aquila, Via Vetoio – Coppito 2

Nature Communications, 2012, vol. 3, issue 1, 1-10

Abstract: Abstract Interleukin-6 (IL-6) and c-Src impair osteoblast maturation in vitro and in vivo. Given the similar effects of these factors, they are likely to establish a functional loop to maintain osteoblasts in a less mature status. Here we describe a pathway whereby c-Src stimulates IL-6 expression through the STAT3 factor, which, in response to IL-6 induces insulin-like growth factor 5 (IGFBP5), a c-Src activating factor that amplifies this loop only in immature osteoblasts. In contrast, in mature osteoblasts, IGFBP5 is enhanced by Runx2, but is no longer able to stimulate c-Src activation, as this tyrosine kinase at this stage is downregulated. We find that the IGFBP5 produced by osteoblasts stimulates osteoclastogenesis and bone resorption, acting as an osteoblast–osteoclast coupling factor. Finally, we demonstrate that the integrated actions of c-Src, IL-6 and IGFBP5 also have a role in vivo. We conclude that this pathway is relevant for bone metabolism, both in physiological and in pathological conditions.

Date: 2012
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms1651 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1651

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1651

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().