Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.
Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.
复制标题
在双膦酸盐治疗后骨转换相关细胞信号传导的双膦酸盐暴露颌骨分析中，Msx-1 受到抑制。
DOI：
10.1111/j.1601-0825.2010.01778.x
复制
发表时间：
2011
期刊：
影响因子：
3.8
通讯作者：
E. Nkenke
中科院分区：
文献类型：
--
作者：
F. Wehrhan;P. Hyckel;Kerstin Amann;Jutta Ries;P. Stockmann;K. Schlegel;F. Neukam;E. Nkenke
目标
骨破坏性疾病治疗包括双膦酸盐和抗核因子κB配体受体激活剂（aRANKL）的抗体。下颌骨坏死（ONJ）是一种副作用。病因病理学模型未能解释其对颌骨的限制。骨增殖转录因子Msx-1只在成熟颌骨中组成型表达。Msx-1的表达可能在二膦酸盐相关ONJ中受损。本研究比较了Msx-1、骨形态发生蛋白（BMP）-2和RANKL在ONJ受累和健康颌骨中的表达。
材料和方法
在ONJ受影响的和健康的颌骨样品（各n = 20）上使用基于自动化化学的碱性磷酸酶-抗碱性磷酸酶方法：细胞数比（标记指数，Bonferroni调整）。实时定量RT-PCR比较Msx-1、BMP-2、RANKL和GAPDH mRNA水平。
结果
与健康骨相比，ONJ中Msx-1（P < 0.03）和RANKL（P < 0.003）的标记指数显著降低，BMP-2的标记指数显著升高（P < 0.02）。ONJ骨中Msx-1的表达降低7倍（P < 0.03），RANKL降低22倍（P < 0.001），BMP-2升高8倍（P < 0.02）。
结论
Msx-1、RANKL抑制和BMP-2诱导与BP和aRANKL诱导的ONJ中的双膦酸盐相关骨硬化和骨重建受损一致。Msx-1抑制提示ONJ在颌骨中的排他性可能的解释。将来应进行骨重建过程中Msx-1- RANKL相互作用的功能分析。
OBJECTIVES
Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone.
MATERIAL AND METHODS
An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels.
RESULTS
Labelling indices were significantly lower for Msx-1 (P < 0.03) and RANKL (P < 0.003) and significantly higher (P < 0.02) for BMP-2 in ONJ compared with healthy bone. Expression was sevenfold lower (P < 0.03) for Msx-1, 22-fold lower (P < 0.001) for RANKL and eightfold higher (P < 0.02) for BMP-2 in ONJ bone.
CONCLUSIONS
Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future.
影响因子：
3.8
作者：
Stefanik D;Sarin J;Lam T;Levin L;Leboy PS;Akintoye SO
通讯作者：
Akintoye SO
影响因子：
--
作者：
H. Ryoo;H. Hoffmann;T. Beumer;Baruch Frenkel;Dwight A. Towler;G. S. Stein;J. Stein;A. J. Wijnen;J. Lian
通讯作者：
H. Ryoo;H. Hoffmann;T. Beumer;Baruch Frenkel;Dwight A. Towler;G. S. Stein;J. Stein;A. J. Wijnen;J. Lian
DOI：
10.1073/pnas.91.26.12887
发表时间：
1994-12-20
影响因子：
11.1
作者：
HOFFMANN, HM;CATRON, KM;STEIN, JL
通讯作者：
STEIN, JL