Regeneracion Tejido Oseo

JOURNAL OF BONE AND MINERAL RESEARCH Volume 24, Number 2, 2009 Published online on October 13, 2008; doi: 10.1359/JBMR.081003 Ó 2009 American Society for Bone and Mineral Research

Skeletal Cell Fate Decisions Within Periosteum and Bone Marrow During Bone Regeneration
´ Celine Colnot

ABSTRACT: Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow depositionof cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Resultsshow that periosteal injuries heal by endochondral ossification, whereas bone marrow injuries heal by intramembranous ossification, indicating that distinct cellular responses occur within these tissues during repair. Next, lineage analyses were used to track the fate of cells derived from periosteum, bone marrow, and endosteum, a subcompartment of the bone marrow. Skeletal progenitor cells werefound to be recruited locally and concurrently from periosteum and/or bone marrow/endosteum during bone repair. Periosteum and bone marrow/endosteum both gave rise to osteoblasts, whereas the periosteum was the major source of chondrocytes. Finally, results show that intrinsic and environmental signals modulate cell fate decisions within these tissues. In conclusion, this study sheds light into theorigins of skeletal stem cells/progenitors during bone regeneration and indicates that periosteum, endosteum, and bone marrow contain pools of stem cells/progenitors with distinct osteogenic and chondrogenic potentials that vary with the tissue environment. J Bone Miner Res 2009;24:274–282. Published online on October 13, 2008; doi: 10.1359/JBMR.081003 Key words: periosteum, bone marrow, bonegraft, in vivo cell lineage, bone repair

INTRODUCTION
ONE REGENERATION IS largely dependent on a successful inflammatory response, revascularization of the injury site, secretion of osteogenic and chondrogenic factors, and remodeling of the extracellular matrix within the damaged and new bone tissues.(1–6) Less is known about the origins of cells that produce bone and cartilage at the injury site.Several potential sources of skeletal stem cells/ progenitors have been identified that may participate in bone repair. Cells may be delivered through the vasculature(7–9) and may be recruited from bone itself(10–14) or tissues immediately adjacent to bone, such as fat, tendon, and muscle.(15–17) Several lines of evidence suggest that the periosteum and the bone marrow are the main local sources ofskeletal stem cells/progenitors for bone repair. Mechanical disruption of the periosteum or bone marrow delays healing,(18,19) presumably by removing the local source of cells. Although cells isolated from the periosteum or bone marrow can differentiate into chondrocytes and/or osteoblasts in vitro,(10,11,13,14) in vivo studies on the chondrogenic and osteogenic potentials of periosteum and bonemarrow are limited.(20–22) Therefore, we still lack direct

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The author states that she has no conflicts of interest.

evidence showing the cellular contribution of periosteum and bone marrow to bone healing. The difficulty in separating the role of various sources of cells during skeletal regeneration arises in part from the intricate structure of bone and the multiple tissues involved. Inthe majority of bone injuries, cortical bone is broken, thereby permitting communication between the periosteum, the bone marrow, and surrounding soft tissues. Moreover, when the physical barrier between bone compartments is disrupted, the healing response in one tissue may impinge on the response in the adjacent tissue through the diffusion of cells and growth factors. The goal of this study was...