Yang Chiming, Frei Hanspeter, Burt Helen M, Rossi Fabio
Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
Biochem Biophys Res Commun. 2009 Mar 20;380(4):791-6. doi: 10.1016/j.bbrc.2009.01.167. Epub 2009 Feb 3.
Bone marrow stromal cells (MSCs) differentiation and proliferation are controlled by numerous growth factors and hormones. Continuous parathyroid hormone (PTH) treatment has been shown to decrease osteoblast differentiation, whereas pulsatile PTH increases osteoblast differentiation. However, the effects of PTH treatments on MSCs have not been investigated. This study showed continuous PTH treatment in the presence of dexamethasone (DEX) promoted osteogenic differentiation of rat MSCs in vitro, as demonstrated by increased alkaline phosphatase (ALP) activity, number of ALP expressing cells, and up-regulation of PTH receptor-1, ALP, and osteocalcin mRNA expressions. In contrast, pulsatile PTH treatment was found to suppress osteogenesis of rat MSCs, possibly by promoting the maintenance of undifferentiated cells. Additionally, the observed effects of PTH were strongly dependent on the presence of DEX. MSC proliferation however was not influenced by PTH independent of treatment regimen and presence or absence of DEX. Furthermore, our work raised the possibility that PTH treatment may modulate stem/progenitor cell activity within MSC cultures.
骨髓基质细胞（MSCs）的分化和增殖受多种生长因子和激素的控制。持续甲状旁腺激素（PTH）治疗已被证明会降低成骨细胞分化，而脉冲式PTH则会增加成骨细胞分化。然而，PTH治疗对MSCs的影响尚未得到研究。本研究表明，在地塞米松（DEX）存在的情况下进行持续PTH治疗可促进大鼠MSCs在体外的成骨分化，这表现为碱性磷酸酶（ALP）活性增加、表达ALP的细胞数量增多以及PTH受体-1、ALP和骨钙素mRNA表达上调。相反，发现脉冲式PTH治疗会抑制大鼠MSCs的成骨作用，可能是通过促进未分化细胞的维持。此外，观察到的PTH效应强烈依赖于DEX的存在。然而，MSCs的增殖不受PTH的影响，与治疗方案以及DEX的存在与否无关。此外，我们的研究提出了PTH治疗可能调节MSCs培养物中干细胞/祖细胞活性的可能性。
