PDF(Pubmed)
Abstract：
Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human NINEIN gene have been linked to Seckel syndrome and to a rare form of skeletal dysplasia. However, the role of ninein in skeletal development remains unknown. Here, we describe a ninein knockout mouse with advanced endochondral ossification during embryonic development. Although the long bones maintain a regular size, the absence of ninein delays the formation of the bone marrow cavity in the prenatal tibia. Likewise, intramembranous ossification in the skull is more developed, leading to a premature closure of the interfrontal suture. We demonstrate that ninein is strongly expressed in osteoclasts of control mice, and that its absence reduces the fusion of precursor cells into syncytial osteoclasts, whereas the number of osteoblasts remains unaffected. As a consequence, ninein-deficient osteoclasts have a reduced capacity to resorb bone. At the cellular level, the absence of ninein interferes with centrosomal microtubule organization, reduces centrosome cohesion, and provokes the loss of centrosome clustering in multinucleated mature osteoclasts. We propose that centrosomal ninein is important for osteoclast fusion, to enable a functional balance between bone-forming osteoblasts and bone-resorbing osteoclasts during skeletal development.
摘要：
Ninein是一种中心体蛋白，与微管锚定和中心体凝聚力有关。人类NINEIN基因突变与Seckel综合征和一种罕见的骨骼发育不良有关。然而,Ninein在骨骼发育中的作用尚不清楚。这里,我们描述了一个ninein基因敲除小鼠，其在胚胎发育过程中具有晚期软骨内骨化。虽然长骨保持着规律的大小,ninein的缺乏会延迟产前胫骨中骨髓腔的形成。同样，颅骨膜内骨化更发达，导致额间缝线过早闭合。我们证明ninein在对照小鼠的破骨细胞中强烈表达，它的缺失减少了前体细胞向合胞破骨细胞的融合，而成骨细胞的数量不受影响。因此,缺乏ninein的破骨细胞吸收骨的能力降低。在细胞层面,Ninein的缺失会干扰中心体微管组织，减少中心体凝聚力，并引起多核成熟破骨细胞中心体聚集的丧失。我们认为中心体ninein对破骨细胞融合很重要，在骨骼发育过程中实现骨形成成骨细胞和骨吸收破骨细胞之间的功能平衡。
