Henriksen K, Leeming D J, Byrjalsen I, Nielsen R H, Sorensen M G, Dziegiel M H, Martin T John, Christiansen C, Qvist P, Karsdal M A
Pharmos Bioscience A/S & Nordic Bioscience A/S, Herlev, DK-2730, Denmark.
Osteoporos Int. 2007 Jun;18(6):751-9. doi: 10.1007/s00198-006-0298-4. Epub 2007 Jan 10.
We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of aged bones.
Osteoclasts resorb aging bone in order to repair damage and maintain the quality of bone. The mechanism behind the targeting of aged bone for remodeling is not clear. We investigated whether bones endogenously possess the ability to control osteoclastic resorption.
To biochemically distinguish aged and young bones; we measured the ratio between the age-isomerized betaCTX fragment and the non-isomerized alphaCTX fragment. By measurement of TRACP activity, CTX release, number of TRACP positive cells and pit area/pit number, we evaluated osteoclastogenesis as well as osteoclast resorption on aged and young bones.
We found that the alphaCTX/betaCTX ratio is 3:1 in young compared to aged bones, and we found that both alpha and betaCTX are released by osteoclasts during resorption. Osteoclastogenesis was augmented on aged compared to young bones, and the difference was enhanced under low serum conditions. We found that mature osteoclasts resorb more on aged than on young bone, despite unchanged adhesion and morphology.
These data indicate that the age of the bone plays an important role in controlling osteoclast-mediated resorption, with significantly higher levels of osteoclast differentiation and resorption on aged bones when compared to young bones.
我们研究了骨骼年龄是否内源性地控制破骨细胞的骨吸收能力,发现破骨细胞优先在老化骨骼上发育并吸收骨组织。这些发现表明骨基质本身在老化骨骼的靶向重塑中发挥作用。
破骨细胞吸收老化骨骼以修复损伤并维持骨质量。老化骨骼靶向重塑背后的机制尚不清楚。我们研究了骨骼是否内源性地具有控制破骨细胞吸收的能力。
为了从生化角度区分老化骨骼和年轻骨骼,我们测量了年龄异构化的βCTX片段与非异构化的αCTX片段之间的比例。通过测量抗酒石酸酸性磷酸酶(TRACP)活性、CTX释放量、TRACP阳性细胞数量以及蚀斑面积/蚀斑数量,我们评估了老化骨骼和年轻骨骼上的破骨细胞生成以及破骨细胞吸收情况。
我们发现,与老化骨骼相比,年轻骨骼中的αCTX/βCTX比例为3:1,并且我们发现破骨细胞在吸收过程中会释放αCTX和βCTX。与年轻骨骼相比,老化骨骼上的破骨细胞生成增加,并且在低血清条件下这种差异会增强。我们发现,尽管黏附力和形态没有变化,但成熟破骨细胞在老化骨骼上的吸收比在年轻骨骼上更多。
这些数据表明,骨骼年龄在控制破骨细胞介导的吸收中起重要作用,与年轻骨骼相比,老化骨骼上破骨细胞分化和吸收的水平显著更高。