Bakker A D, Klein-Nulend J, Tanck E, Heyligers I C, Albers G H, Lips P, Burger E H
Department of Oral Cell Biology, ACTA-VU/UvA, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
Osteoporos Int. 2006;17(6):827-33. doi: 10.1007/s00198-006-0072-7. Epub 2006 Mar 25.
Osteoporosis (OP) and osteoarthritis (OA) are both common diseases in the elderly, but remarkably seldom coexist. The bone defects that are related to both diseases develop with increasing age, which suggests that they are related to some form of imperfect bone remodeling. Current opinion holds that the bone remodeling process is supervised by bone cells that respond to mechanical stimuli. An imperfect response of bone cells to mechanical stimuli might thus relate to imperfect bone remodeling, which could eventually lead to a lack bone mass and strength, such as in OP patients.
To investigate whether the cellular response to mechanical stress differs between OP and OA patients, we compared the response of bone cells from both groups to fluid shear stress of increasing magnitude. Bone cells from 9 female OP donors (age 60-90 year) and 9 female age-matched OA donors were subjected to pulsating fluid flow (PFF) of low (0.4+/-0.1 Pa at 3 Hz), medium (0.6+/-0.3 Pa at 5 Hz), or high shear stress (1.2+/-0.4 at 9Hz), or were kept under static culture conditions.
We found subtle differences in the shear-stress response of the two groups, measured as nitric oxide (NO) and prostaglandin E2 (PGE2) production. The NO-response to shear stress was higher in the OP than the OA cells, while the PGE2-response was higher in the OA cells.
Assuming that NO and PGE2 play a role in cell-cell communication during remodeling, these results suggest that slight differences in mechanotransduction might relate to the opposite bone defects in osteoporosis and osteoarthritis.
骨质疏松症(OP)和骨关节炎(OA)都是老年人常见的疾病,但极少同时存在。与这两种疾病相关的骨缺陷会随着年龄增长而发展,这表明它们与某种形式的骨重塑不完善有关。目前的观点认为,骨重塑过程由对机械刺激作出反应的骨细胞监督。因此,骨细胞对机械刺激的不完善反应可能与骨重塑不完善有关,最终可能导致骨量和骨强度不足,比如骨质疏松症患者的情况。
为了研究骨质疏松症患者和骨关节炎患者的细胞对机械应力的反应是否存在差异,我们比较了两组骨细胞对不同大小流体剪切应力的反应。来自9名女性骨质疏松症捐赠者(年龄60 - 90岁)和9名年龄匹配的女性骨关节炎捐赠者的骨细胞,分别接受低(3Hz时0.4±0.1Pa)、中(5Hz时0.6±0.3Pa)或高剪切应力(9Hz时1.2±0.4)的脉动流体流(PFF)处理,或置于静态培养条件下。
我们发现两组在剪切应力反应方面存在细微差异,以一氧化氮(NO)和前列腺素E2(PGE2)的产生量来衡量。骨质疏松症患者的骨细胞对剪切应力的NO反应高于骨关节炎患者的骨细胞,而骨关节炎患者的骨细胞对剪切应力的PGE2反应更高。
假设NO和PGE2在重塑过程中的细胞间通讯中发挥作用,则这些结果表明,机械转导方面的细微差异可能与骨质疏松症和骨关节炎中相反的骨缺陷有关。