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Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2
C M Champagne1, J Takebe, S Offenbacher
1Dental Research Center, University of North Carolina School of Dentistry, Chapel Hill, NC 27599-7450, USA.
Bone
|January 17, 2002
Summary
Macrophages express bone morphogenetic proteins (BMPs), crucial for bone healing. This study reveals macrophages contribute to osteoinduction, a key factor in bone regeneration and osseous wound healing.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Biochemistry
Background:
- Bone wound healing relies on bone morphogenetic proteins (BMPs) for osteoinductive signals.
- The cellular sources of these critical osteoinductive signals remain incompletely understood.
- Macrophages are central to cutaneous wound healing, prompting investigation into their role in osseous healing.
Purpose of the Study:
- To investigate the expression of BMPs by macrophages.
- To assess the contribution of macrophage-derived factors to early bone formation in vitro.
- To understand the physiological regulation of macrophage osteoinductive signaling.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) to detect BMP-2 and BMP-6 synthesis in human and murine macrophages.
- In vitro culture system using conditioned media from macrophages and human mesenchymal stem cells (hMSCs).
- Assay of alkaline phosphatase (ALP) activity in hMSCs as a marker of osteogenic differentiation.
- Stimulation of macrophages with lipopolysaccharide (LPS) or macrophage chemotactic peptide-1 (MCP-1) to model physiological conditions.
Main Results:
- Macrophages synthesize BMP-2 and BMP-6.
- Conditioned media from macrophages increased alkaline phosphatase expression in hMSCs, an effect blocked by anti-BMP-2 and anti-transforming growth factor-beta1 (TGF-beta1) antibodies.
- Pro-inflammatory stimulation with LPS reduced macrophage BMP-2 expression and abrogated the osteoinductive capacity of their conditioned media.
- LPS stimulation induced the release of tumor necrosis factor-alpha (TNF-alpha) from macrophages.
Conclusions:
- Macrophages express BMP-2 and BMP-6, suggesting a role in osteoinduction.
- Macrophage-derived factors, particularly BMP-2, contribute to early bone formation.
- Macrophage BMP-2 expression is subject to physiological regulation, being downregulated by pro-inflammatory stimuli.
- Macrophages are a potential key cellular player in osseous wound healing and osteogenesis.