Villa Anna, Guerrini Matteo M, Cassani Barbara, Pangrazio Alessandra, Sobacchi Cristina
Istituto di Tecnologie Biomediche, CNR, via Cervi 93, Segrate, Italy.
Calcif Tissue Int. 2009 Jan;84(1):1-12. doi: 10.1007/s00223-008-9196-4. Epub 2008 Dec 12.
Human recessive osteopetrosis (ARO) represents a group of diseases in which, due to a defect in osteoclasts, bone resorption is prevented. The deficit could arise either from failure in osteoclast differentiation or from inability to perform resorption by mature, multinucleated, but nonfunctional cells. Historically, osteopetrosis due to both these mechanisms was found in spontaneous and artificially created mouse mutants, but the first five genes identified in human ARO (CA-II, TCIRG1, ClCN7, OSTM1, and PLEKHM1) were all involved in the effector function of mature osteoclasts, being linked to acidification of the cell/bone interface or to intracellular processing of the resorbed material. Differentiation defects in human ARO have only recently been described, following the identification of mutations in both RANKL and RANK, which define a new form of osteoclast-poor ARO, as expected from biochemical, cellular, and animal studies. The molecular dissection of ARO has prognostic and therapeutic implications. RANKL-dependent patients, in particular, represent an interesting subset which could benefit from mesenchymal cell transplant and/or administration of soluble RANKL cytokine.
人类隐性骨硬化症（ARO）是一组由于破骨细胞缺陷而导致骨吸收受阻的疾病。这种缺陷可能源于破骨细胞分化失败，或者源于成熟的多核但无功能的细胞无法进行吸收。从历史上看，由于这两种机制导致的骨硬化症在自发产生和人工培育的小鼠突变体中都有发现，但在人类ARO中鉴定出的前五个基因（CA-II、TCIRG1、ClCN7、OSTM1和PLEKHM1）都与成熟破骨细胞的效应功能有关，与细胞/骨界面的酸化或吸收物质的细胞内处理有关。在鉴定出RANKL和RANK的突变后，人类ARO中的分化缺陷才在最近被描述，正如生化、细胞和动物研究预期的那样，这定义了一种新的破骨细胞缺乏型ARO。ARO的分子剖析具有预后和治疗意义。特别是，依赖RANKL的患者是一个有趣的亚组，可能从间充质细胞移植和/或可溶性RANKL细胞因子给药中受益。
