Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research Ulm, University of Ulm, Ulm, Germany.
J Cell Biochem. 2010 Feb 1;109(2):347-55. doi: 10.1002/jcb.22406.
Osteoclast activity has traditionally been regarded as restricted to bone resorption but there is some evidence that also non-resorbing osteoclasts might influence osteoblast activity. The aim of the present study was to further investigate the hypothesis of an anabolic function of non-resorbing osteoclasts by investigating their capability to recruit mesenchymal stem cells (MSC) and to provoke their differentiation toward the osteogenic lineage. Bone-marrow-derived human MSC were exposed to conditioned media (CM) derived from non-resorbing osteoclast cultures, which were generated from human peripheral blood monocytes. Osteogenic marker genes (transcription factor Runx2, bone sialoprotein, alkaline phosphatase (AP), and osteopontin) were significantly increased. Osteogenic differentiation (OD) was also proved by von Kossa and AP staining occurred in the same range as in MSC cultures stimulated with osteogenic supplements. Chemotactic responses of MSC were measured with a modified Boyden chamber assay. CM from osteoclast cultures induced a strong migratory response in MSC, which was greatly reduced in the presence of an anti-human platelet-derived growth factor (PDGF) receptor beta antibody. Correspondingly, significantly increased PDGF-BB concentrations were measured in the CM using a PDGF-BB immunoassay. CM derived from mononuclear cell cultures did not provoke MSC differentiation and had a significantly lower migratory effect on MSC suggesting that the effects were specifically mediated by osteoclasts. In conclusion, it can be suggested that human non-resorbing osteoclasts induce migration and OD of MSC. While effects on MSC migration might be mainly due to PDGF-BB, the factors inducing OD remain to be elucidated.
破骨细胞的活性传统上被认为仅限于骨吸收，但有一些证据表明，不进行骨吸收的破骨细胞也可能影响成骨细胞的活性。本研究的目的是通过研究其招募间充质干细胞 (MSC) 的能力，并促使其向成骨谱系分化，进一步验证不进行骨吸收的破骨细胞具有合成代谢功能的假说。骨髓来源的人 MSC 暴露于非破骨细胞培养物的条件培养基 (CM) 中，这些非破骨细胞由人外周血单核细胞生成。成骨标志物基因（转录因子 Runx2、骨涎蛋白、碱性磷酸酶 (AP) 和骨桥蛋白）显著增加。成骨分化 (OD) 也通过 von Kossa 和 AP 染色得到证实，其发生的范围与用成骨补充剂刺激的 MSC 培养物相同。使用改良的 Boyden 室测定法测量 MSC 的趋化反应。来自破骨细胞培养物的 CM 诱导 MSC 产生强烈的迁移反应，而在存在抗人血小板衍生生长因子 (PDGF) 受体 β 抗体的情况下，该反应大大降低。相应地，使用 PDGF-BB 免疫测定法在 CM 中测量到 PDGF-BB 浓度显著增加。单核细胞培养物衍生的 CM 不会引发 MSC 分化，并且对 MSC 的迁移作用明显较低，这表明这些作用是由破骨细胞特异性介导的。总之，可以认为人类非破骨型破骨细胞诱导 MSC 的迁移和 OD。虽然对 MSC 迁移的影响可能主要归因于 PDGF-BB，但诱导 OD 的因素仍有待阐明。
