Skip to main content
 
Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
Stanford Health Care

CCL2, CCL5 and IGF-1 Participate in The Immunomodulation of Osteogenesis during M1/M2 Transition In Vitro.

CCL2, CCL5 and IGF-1 Participate in The Immunomodulation of Osteogenesis during M1/M2 Transition In Vitro. Journal of biomedical materials research. Part A Córdova, L. A., Loi, F. n., Lin, T. H., Gibon, E. n., Pajarinen, J. n., Nabeshima, A. n., Lu, L. n., Yao, Z. n., Goodman, S. B. 2017

Abstract

The modulation of macrophage phenotype from pro-inflammatory (M1) to tissue healing (M2) via exogenous addition of interleukin-4 (IL-4) facilitates osteogenesis; however, the molecular mediators underlying this phenomenon remain unknown. This study characterizes the IL-4-dependent paracrine crosstalk between macrophages and osteoprogenitors and its effect on osteogenesis in vitro. Primary murine M1 were co-cultured with MC3T3 cells (M1-MC3T3) in both transwell plates and direct co-cultures. To modulate M1 to M2, M1-MC3T3 were treated with IL-4 (20ng/mL) at day 3 after seeding (M1+IL-4-MC3T3). Selected molecular targets were assessed at days 3 and 6 after seeding at protein and mRNA levels. Mineralization was assessed at day 21. Transwell M1+IL-4-MC3T3 significantly enhanced the secretion of CCL2/MCP-1, IGF-1 and to a lesser degree, CCL5/RANTES at day 6. At day 3, alkaline phosphatase (Alpl) was up-regulated in direct M1-MC3T3. At day 6, Smurf2 and Insulin growth factor-1 (Igf-1) were down-regulated and up-regulated respectively in direct M1+IL-4-MC3T3. Finally, M1+IL-4-MC3T3 increased bone matrix mineralization compared with MC3T3 cells in transwell, but this was significantly less than M1-MC3T3. Taken together, macrophage subtypes enhanced the osteogenesis in transwell setting and the transition from M1 to M2 was associated with an increase in bone anabolic factors CCL2/MCP-1, CCL5/RANTES and IGF-1 in vitro. This article is protected by copyright. All rights reserved.

View details for PubMedID 28782174