Circulating Osteoblast-Lineage Cells
http://www.100md.com
《新英格兰医药杂志》
To the Editor: The study by Eghbali-Fatourechi et al. (May 12 issue)1 suggests the presence of circulating osteoblasts that potentially contribute to physiological bone formation. In addition to its association with bone modeling and remodeling, as Canalis discusses in the accompanying editorial,2 calcification can be observed in blood vessels and heart valves as a common complication of atherosclerosis, diabetes, and end-stage renal disease and is generally considered to be a significant predictor of adverse clinical events. Extraosseous calcification seems to be an active, cell-mediated process within bone-like tissues with marrow, cartilaginous tissue, and osteoblast-like cells.3 Since naive nonosseous tissues contain no osteoblasts, the origin of ectopic osteoblasts remains unclear. Recent evidence suggests that circulating progenitors contribute to the accumulation of smooth-muscle cells in atherosclerotic lesions.4,5 It may be plausible that the circulating osteoblast-lineage cells participate in the pathogenesis of ectopic ossification. It is consistent with this notion that extraosseous calcification and osteoporosis tend to occur in the same patients and correlate in severity. Deregulated mobilization, homing, and proliferation of circulating osteoblasts may account for both diseases.3 Therefore, quantification of circulating osteoblasts in patients with ectopic calcification is worthy of investigation.
Masataka Sata, M.D.
Kimie Tanaka, M.D.
Ryozo Nagai, M.D.
University of Tokyo Graduate School of Medicine
Tokyo 113-8655, Japan
msata-circ@umin.ac.jp
References
Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med 2005;352:1959-1966.
Canalis E. The fate of circulating osteoblasts. N Engl J Med 2005;352:2014-2016.
Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol 2004;24:1161-1170.
Sata M, Saiura A, Kunisato A, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med 2002;8:403-409.
Caplice NM, Bunch TJ, Stalboerger PG, et al. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proc Natl Acad Sci U S A 2003;100:4754-4759.
The authors reply: Circulating mesenchymal cells may indeed participate in ectopic ossification. Mechanisms regulating vascular calcification involve paracrine osteogenic signals (i.e., the bone morphogenetic protein BMP-2 and Wnt proteins)1; whether these osteogenic stimuli act primarily on resident stem cells in the vasculature to induce osteogenic differentiation1 or recruit circulating myofibroblast2 or osteoblastic progenitors at sites of injury is unknown. These possibilities are not mutually exclusive. For example, since circulating osteoblastic cells are already partially differentiated, they may immediately participate in the response to injury, whether in the vascular tree, fractured bone, or other tissues. By contrast, osteogenic differentiation of resident stem cells at sites of injury may require some time (i.e., weeks); thus, committed osteoprogenitors in the circulation may constitute the early response to injury and then be relieved by progenitors recruited from the local tissues. Accordingly, there is now evidence supporting the notion that bone marrow harbors subpopulations of tissue-committed cells that participate in the response to injury in a variety of organs3; in addition, infused bone marrow stromal cells localize to the fracture callus in mice but largely are replaced by host osteoblastic cells within eight weeks after fracture.4
Guiti Z. Eghbali-Fatourechi, M.D.
Sundeep Khosla, M.D.
Mayo Clinic College of Medicine
Rochester, MN 55905
khosla.sundeep@mayo.edu
References
Shao JS, Cheng SL, Pingsterhaus JM, Charlton-Kachigian N, Loewy AP, Towler DA. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. J Clin Invest 2005;115:1210-1220.
Simper D, Stalboerger PG, Panetta CJ, Wang S, Caplice NM. Smooth muscle progenitor cells in human blood. Circulation 2002;106:1199-1204.
Kucia M, Ratajczak J, Ratajczak MZ. Are bone marrow stem cells plastic or heterogenous -- that is the question. Exp Hematol 2005;33:613-623.
Devine MJ, Mierisch CM, Jang E, Anderson PC, Balian G. Transplanted bone marrow cells localize to fracture callus in a mouse model. J Orthop Res 2002;20:1232-1239.
Masataka Sata, M.D.
Kimie Tanaka, M.D.
Ryozo Nagai, M.D.
University of Tokyo Graduate School of Medicine
Tokyo 113-8655, Japan
msata-circ@umin.ac.jp
References
Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med 2005;352:1959-1966.
Canalis E. The fate of circulating osteoblasts. N Engl J Med 2005;352:2014-2016.
Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol 2004;24:1161-1170.
Sata M, Saiura A, Kunisato A, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med 2002;8:403-409.
Caplice NM, Bunch TJ, Stalboerger PG, et al. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proc Natl Acad Sci U S A 2003;100:4754-4759.
The authors reply: Circulating mesenchymal cells may indeed participate in ectopic ossification. Mechanisms regulating vascular calcification involve paracrine osteogenic signals (i.e., the bone morphogenetic protein BMP-2 and Wnt proteins)1; whether these osteogenic stimuli act primarily on resident stem cells in the vasculature to induce osteogenic differentiation1 or recruit circulating myofibroblast2 or osteoblastic progenitors at sites of injury is unknown. These possibilities are not mutually exclusive. For example, since circulating osteoblastic cells are already partially differentiated, they may immediately participate in the response to injury, whether in the vascular tree, fractured bone, or other tissues. By contrast, osteogenic differentiation of resident stem cells at sites of injury may require some time (i.e., weeks); thus, committed osteoprogenitors in the circulation may constitute the early response to injury and then be relieved by progenitors recruited from the local tissues. Accordingly, there is now evidence supporting the notion that bone marrow harbors subpopulations of tissue-committed cells that participate in the response to injury in a variety of organs3; in addition, infused bone marrow stromal cells localize to the fracture callus in mice but largely are replaced by host osteoblastic cells within eight weeks after fracture.4
Guiti Z. Eghbali-Fatourechi, M.D.
Sundeep Khosla, M.D.
Mayo Clinic College of Medicine
Rochester, MN 55905
khosla.sundeep@mayo.edu
References
Shao JS, Cheng SL, Pingsterhaus JM, Charlton-Kachigian N, Loewy AP, Towler DA. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. J Clin Invest 2005;115:1210-1220.
Simper D, Stalboerger PG, Panetta CJ, Wang S, Caplice NM. Smooth muscle progenitor cells in human blood. Circulation 2002;106:1199-1204.
Kucia M, Ratajczak J, Ratajczak MZ. Are bone marrow stem cells plastic or heterogenous -- that is the question. Exp Hematol 2005;33:613-623.
Devine MJ, Mierisch CM, Jang E, Anderson PC, Balian G. Transplanted bone marrow cells localize to fracture callus in a mouse model. J Orthop Res 2002;20:1232-1239.