Pei W, Yoshimine Y, Heersche J N M
Faculty of Dentistry, University of Toronto, 124 Edward street, Ontario MSG 1G6, Canada.
Calcif Tissue Int. 2003 Feb;72(2):124-34. doi: 10.1007/s00223-001-2052-4. Epub 2002 Nov 6.
The purpose of this investigation was to establish whether or not dexamethasone (Dex)-dependent osteoprogenitors with sufficient proliferative capacity to form a colony of bone-forming osteoblasts could be identified in cell populations isolated from adult human bone. This question is relevant because of the ongoing controversy regarding the effects of dexamethasone on bone formation in humans, the clearly different effects of dexamethasone on osteoprogenitor differentiation in mouse vs. rat bone cell populations, and the related question of whether observations in either rat or mouse systems are applicable to human systems. To answer the question, we isolated cell populations from distal femoral cancellous bone of 8 female patients with osteoarthritis and quantitated the number of Dex-dependent osteoprogenitors in these populations by counting the number of osteoblastic colonies forming bone (bone nodules) or unmineralized bone matrix (osteoid nodules). Dex increased alkaline phosphatase (AP) content in all populations, induced bone nodule formation in 2 of the 8 populations, and induced formation of AP-positive clusters of cells with osteoblastic morphology in one. Treatment with 1,25-dihydroxyvitamin D3 increased osteocalcin (OC) production in the nodule forming populations, but not in the non-nodule-forming populations. Our results thus establish that Dex-dependent osteoprogenitors with sufficient proliferative capacity to form bone or osteoid nodules are present in cell populations derived from adult human bone. They also show that frozen primary human bone cell populations that have been characterized previously in terms of the number of Dex-dependent osteoprogenitors present can be used to further study the characteristics of such progenitors.
本研究的目的是确定从成年人类骨骼分离的细胞群体中是否能识别出具有足够增殖能力以形成成骨成骨细胞集落的地塞米松（Dex）依赖性骨祖细胞。这个问题很重要，因为关于地塞米松对人类骨形成的影响存在持续争议，地塞米松对小鼠和大鼠骨细胞群体中骨祖细胞分化的影响明显不同，以及大鼠或小鼠系统中的观察结果是否适用于人类系统的相关问题。为了回答这个问题，我们从8名骨关节炎女性患者的股骨远端松质骨中分离细胞群体，并通过计数形成骨（骨结节）或未矿化骨基质（类骨质结节）的成骨细胞集落数量来定量这些群体中Dex依赖性骨祖细胞的数量。地塞米松增加了所有群体中的碱性磷酸酶（AP）含量，在8个群体中的2个中诱导了骨结节形成，在1个中诱导形成了具有成骨细胞形态的AP阳性细胞簇。用1,25 - 二羟基维生素D3处理增加了形成结节的群体中的骨钙素（OC）产生，但在不形成结节的群体中没有增加。因此，我们的结果表明，具有足够增殖能力以形成骨或类骨质结节的Dex依赖性骨祖细胞存在于源自成年人类骨骼的细胞群体中。它们还表明，先前已根据存在的Dex依赖性骨祖细胞数量进行表征的冷冻原代人类骨细胞群体可用于进一步研究此类祖细胞的特征。
