Generation of novel bone forming cells (monoosteophils) from the cathelicidin-derived peptide LL-37 treated monocytes
| Autor: | John E. Shively, Zhifang Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Bone sialoprotein
Time Factors Immunology/Innate Immunity Osteoclasts lcsh:Medicine Mice SCID Monocytes Mice 0302 clinical medicine Mice Inbred NOD Osteogenesis Microscopy Phase-Contrast Osteonectin Osteopontin lcsh:Science Cells Cultured Tartrate-resistant acid phosphatase 0303 health sciences Multidisciplinary biology Osteoblast Cell Differentiation 3. Good health Cell biology medicine.anatomical_structure RANKL Cytokines Immunology/Leukocyte Development Research Article Cell Survival Osteocalcin Bone healing Osteocytes Cell Line 03 medical and health sciences Osteoclast Cathelicidins medicine Animals Humans 030304 developmental biology Cell Proliferation Osteoblasts Dose-Response Relationship Drug Macrophages Mesenchymal stem cell lcsh:R Dendritic Cells Immunology/Leukocyte Activation Immunology biology.protein Microscopy Electron Scanning Cell Biology/Morphogenesis and Cell Biology lcsh:Q 030215 immunology Antimicrobial Cationic Peptides |
| Zdroj: | PLoS ONE, Vol 5, Iss 11, p e13985 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Background Bone generation and maintenance involve osteoblasts, osteoclasts, and osteocytes which originate from unique precursors and rely on key growth factors for differentiation. However, an incomplete understanding of bone forming cells during wound healing has led to an unfilled clinical need such as nonunion of bone fractures. Since circulating monocytes are often recruited to sites of injury and may differentiate into various cell types including osteoclasts, we investigated the possibility that circulating monocytes in the context of tissue injury may also contribute to bone repair. In particular, we hypothesized that LL-37 (produced from hCAP-18, cathelicidin), which recruits circulating monocytes during injury, may play a role in bone repair. Methods and Findings Treatment of monocytes from blood with LL-37 for 6 days resulted in their differentiation to large adherent cells. Growth of LL-37-differentiated monocytes on osteologic discs reveals bone-like nodule formation by scanning electron microscopy (SEM). In vivo transplantation studies in NOD/SCID mice show that LL-37-differentiated monocytes form bone-like structures similar to endochondral bone formation. Importantly, LL-37-differentiated monocytes are distinct from conventional monocyte-derived osteoclasts, macrophages, and dendritic cells and do not express markers of the mesenchymal stem cells (MSC) lineage, distinguishing them from the conventional precursors of osteoblasts. Furthermore, LL-37 differentiated monocytes express intracellular proteins of both the osteoblast and osteoclast lineage including osteocalcin (OC), osteonectin (ON), bone sialoprotein II (BSP II), osteopontin (OP), RANK, RANKL, MMP-9, tartrate resistant acid phosphatase (TRAP), and cathepsin K (CK). Conclusion Blood derived monocytes treated with LL-37 can be differentiated into a novel bone forming cell that functions both in vitro and in vivo. We propose the name monoosteophil to indicate their monocyte derived lineage and their bone forming phenotype. These cells may have wide ranging implications in the clinic including repair of broken bones and treatment of osteoporosis. |
| Databáze: | OpenAIRE |
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