Abstract
Mesenchymal progenitors within bone marrow have multiple differentiation potential and play an essential role in the maintenance of adult skeleton homeostasis. Mesenchymal progenitors located in bone regions other than the bone marrow also display bone-forming properties. However, owing to the differences in each distinct microenvironment, the mesenchymal characteristics of skeletal progenitor cells within different regions of long bones may show some differences. In order to clearly elucidate these differences, we performed a comparative study on mesenchymal progenitors from different regions of long bones. Here, we isolated mesenchymal progenitors from the periosteum, endosteum, and bone marrow of rat long bones. The three groups exhibited similar cellular morphologies and expressed the typical surface markers associated with mesenchymal stem cells. Interestingly, after cell proliferation assays and bidirectional differentiation analysis, periosteal mesenchymal progenitors showed a higher proliferative ability and adipogenic differentiation potential. In contrast, endosteal mesenchymal progenitors were more prone to osteogenic differentiation. Using in vitro osteoclast culture systems, conditioned media from different mesenchymal progenitor cultures were used to induce osteoclastic differentiation. Osteoclast formation was found to be significantly promoted by the secretion of RANKL and IL-6 by endosteal progenitors. Overall, our results provide strong evidence for the importance of selecting the appropriate source of skeletal progenitors for applications in future skeleton regeneration therapies.
Highlights
Mesenchymal stem cells (MSCs) or mesenchymal progenitors (MPs) are plastic-adherent fibroblast-like cells that are able to form colony-forming unit-fibroblasts (CFUFs) [1, 2]
A total of 94.4% of CD90+CD34-CD11b-CD45- cells were detected in the endosteal MP (E-MP) group, which is higher than that in the periosteal MP (P-MP) group (91.5%) and that in the marrow MP (M-MP) group (85.9%) (Figure 1(c))
In 1968, Friedenstein et al first reported the presence of adherent fibroblast-like stromal cells with osteogenic potential in bone marrow; MSCs or MPs were later identified [1, 2]
Summary
Mesenchymal stem cells (MSCs) or mesenchymal progenitors (MPs) are plastic-adherent fibroblast-like cells that are able to form colony-forming unit-fibroblasts (CFUFs) [1, 2]. According to the International Society for Cellular Therapy (ISCT), to identify and characterize MPs, they should express several cell surface markers, such as CD90, CD105, and CD73 and should not express CD45, CD34, CD14 or CD11b, CD79a or CD19, and HLA-DR [3, 4]. MPs have immunosuppressive effects [8]. These characteristics make MPs a promising resource for regenerative medicine, clinical cell therapies, and tissue engineering. Recent studies have identified mouse and human skeletal stem cells (SSCs) that are enriched in the growth plate and express specific surface markers. In addition to bone marrow, the periosteum and endosteum are membranous structures that contain MPs. The periosteum is composed of two layers: the outer “fibrous” layer and the inner “cambium” layer [17]. The outer layer contains attachment points for tendons, ligaments, and muscles; it
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