PMID- 11792561 OWN - NLM STAT- MEDLINE DCOM- 20020429 LR - 20220321 IS - 8756-3282 (Print) IS - 1873-2763 (Linking) VI - 30 IP - 1 DP - 2002 Jan TI - Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. PG - 26-31 AB - Bone wound healing requires osteoinductive signals that are attributed to (the) bone morphogenetic proteins (BMPs). The cellular origin of such osteoinductive signals has only been partially elucidated. Because of the central role of the macrophage in cutaneous wound healing, we hypothesized that the macrophage could play a similar role in osseous healing. It was the aim of the present investigation to examine the possible expression of BMP by the macrophage, and to evaluate the contribution of macrophage products to an early step of bone formation modeled in an in vitro culture system. The synthesis of BMP-2 and BMP-6 by cultured human and murine macrophages was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). When human mesenchymal stem cells (hMSCs) were grown in conditioned media from J774A.1 cells, alkaline phosphatase expression increased. This induction was blocked by anti-BMP-2 antibody and by anti-transforming growth factor-beta1 (TGF-beta1) antibody. Modeling of the macrophage expression of osteoinductive signals by potential physiological situations was evaluated by treatments with lipopolysaccharide (LPS) or macrophage chemotactic peptide-1 (MCP-1). Macrophage BMP-2 expression was reduced by proinflammatory LPS stimulation (which was confirmed to induce release of the proinflammatory cytokine, TNF-alpha), and conditioned media from LPS-treated macrophages had no ability to increase alkaline phosphatase activity in hMSCs. This first study of macrophage BMP-2 expression indicates that the macrophage is capable of physiological regulation consistent with a key role in osteoinduction for osseous wound healing. FAU - Champagne, C M AU - Champagne CM AD - Dental Research Center, University of North Carolina School of Dentistry, Chapel Hill, NC 27599-7450, USA. FAU - Takebe, J AU - Takebe J FAU - Offenbacher, S AU - Offenbacher S FAU - Cooper, L F AU - Cooper LF LA - eng PT - Journal Article PL - United States TA - Bone JT - Bone JID - 8504048 RN - 0 (BMP2 protein, human) RN - 0 (BMP6 protein, human) RN - 0 (Bmp2 protein, mouse) RN - 0 (Bmp6 protein, mouse) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Bone Morphogenetic Protein 6) RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Culture Media, Conditioned) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/biosynthesis MH - Animals MH - Bone Morphogenetic Protein 2 MH - Bone Morphogenetic Protein 6 MH - Bone Morphogenetic Proteins/*biosynthesis/genetics MH - Cell Differentiation MH - Cell Line MH - Culture Media, Conditioned MH - Fracture Healing/genetics/*physiology MH - Gene Expression MH - Humans MH - Lipopolysaccharides/pharmacology MH - Macrophages/*physiology MH - Mice MH - Models, Biological MH - Osteoblasts/cytology MH - Osteogenesis/genetics/physiology MH - RNA, Messenger/genetics/metabolism MH - Signal Transduction MH - Stem Cells/cytology MH - *Transforming Growth Factor beta MH - Tumor Necrosis Factor-alpha/biosynthesis EDAT- 2002/01/17 10:00 MHDA- 2002/05/01 10:01 CRDT- 2002/01/17 10:00 PHST- 2002/01/17 10:00 [pubmed] PHST- 2002/05/01 10:01 [medline] PHST- 2002/01/17 10:00 [entrez] AID - S875632820100638X [pii] AID - 10.1016/s8756-3282(01)00638-x [doi] PST - ppublish SO - Bone. 2002 Jan;30(1):26-31. doi: 10.1016/s8756-3282(01)00638-x.