Exposure to pro-inflammatory cytokines upregulates MMP-9 synthesis by mesenchymal stem cells-derived osteoprogenitors

D. Ben David, A. Z. Reznick, S. Srouji, E. Livne

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


An intimate interplay exists between the bone and the immune system, which has been recently termed osteoimmunology. The activity of immune cells affects the intrinsic balance of bone mineralization and resorption carried out by the opposing actions of osteoblasts and osteoclasts. The aim of this study was to determine the possible interaction between inflammatory-induced conditions and matrix metalloproteinases-2,-9 (MMP-2,-9) synthesis and secretion by bone marrow-derived osteoprogenitor cells during advanced stages of osteogenesis. Rat bone marrow-derived mesenchymal stem cells (MSCs) were cultured in the presence of osteogenic supplements in order to direct the cells towards the osteogenic differentiation lineage. At the late stages of osteogenesis, assessed by histochemistry, immunohistochemistry and RT-PCR, cultures were exposed to pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1alpha (IL-1α). Biochemical, histochemical and molecular biology techniques were used to discern the influence of pro-inflammatory cytokines on MMP-2,-9 synthesis and secretion. Results indicated that MMP-9 synthesis and secretion were significantly induced after exposure to the cytokines (TNF-α, IL-1α) treatment, while MMP-2 levels remained unchanged. These results indicate that in response to inflammatory processes, osteoblasts, in addition to osteoclasts, can also be involved and contribute to the process of active bone resorption by secretion and activation of MMPs.

Original languageEnglish
Pages (from-to)589-597
Number of pages9
JournalHistochemistry and Cell Biology
Issue number5
StatePublished - May 2008
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments This work has been supported by the Israel Ministry of Commerce, Magnet Grant No. 2007992 and by Joint-Brook-dale Gerontology Institute, and a grant from the Krol Founadtion of Barnegat NJ. USA to AZR. The excellent technical work of Mrs Pessia Schenzer and Mrs Janette Zavin is also acknowledged.


  • Bone
  • Inflammation
  • Matrix metalloproteinase-2,-9
  • Mesenchymal stem cells
  • Osteoprogenitors


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