REGULATION OF OSTEOCLASTIC BONE RESORPTION BY RHO

当机械力作用在牙齿上时，牙周组织就承受了机械应力。许多骨细胞位于骨基质中，通过细胞质突起和间隙连接与骨表面的成骨细胞以及骨基质中的成骨细胞相互沟通。通过对机械应力的检测，推测这种细胞网络对机械负载环境的适应具有一定的重要功能。为了探讨骨细胞在骨吸收中的作用，我们研究了纯化的鸡骨细胞衍生蛋白（ODP）和rho - gtp解离抑制剂（Rho-GDI）对骨吸收的影响。最近，我们在没有成骨细胞和间质细胞的情况下，利用M-CSF和人可溶性RANKL （sRANKL）建立了一个培养系统，提供来自外周血单核细胞（PMBC）的成熟破骨细胞。fitc标记的α -肌动素预微注射到人破骨细胞中，更多地与排列在细胞周围的足小体结合。虽然注射缓冲液后仍可观察到足小体，但微注射ODP和Rho-GDI可在注射后30分钟内引起足小体的破坏。此外，这两种蛋白都能显著抑制窝的形成，而骨细胞的条件培养基则没有影响。本研究还关注了一种新的半胱氨酸蛋白酶cathepsin K，它有望在破骨细胞中特异性表达，并在破骨细胞骨吸收中发挥重要作用。我们通过检测组织蛋白酶K mRNA的表达变化和牙槽骨的组织学变化，研究了正畸牙齿运动过程中牙槽骨重塑的机制。因此，进一步了解破骨细胞的分化和功能机制，将有助于更详细地了解正畸牙齿运动和牙周组织机械应力反应的基础。少

At the time when a mechanical force is applied onto the tooth, mechanical stress is loaded on the periodontal tissues. A number of osteocytes are located in the bone matrix, communicating each other, as well as with the osteoblasts on the bone surface, via cytoplasmatic processes and gap junctions. Such a cellular network is speculated to have certain important functions for the adaptation to a mechanical loaded environment by the detection of mechanical stress.In the present study, in order to investigate the role of osteocytes in bone resorption, we examined the effects of purified chick osteocyte-derived protein (ODP) and Rho-GTP-dissociation inhibitor (Rho-GDI) on bone resorption. Recently, we established a culture system which provided with human mature osteoclasts from peripheral mononuclear blood cells (PMBC) by using M-CSF and human soluble RANKL (sRANKL) in the absence of osteoblasts and stromal cells. FITC-labelled alpha-actinin pre-microinjected into human osteoclasts was in … More corporated into podosomes which lined the periphery of the cells. Although the podosomes were still observed after the injection of buffer, microinjection of ODP and Rho-GDI caused disruption of podosomes within 30 min of injection. Furthermore, both proteins markedly inhibited pit formation, whereas the conditioned medium of osteocytes had no effect.This study has also focused on a novel cysteine proteinase, cathepsin K, which is through to be specifically expressed in osteoclasts and plays an important part in osteoclastic bone resorption. We have investigated the mechanism of alveolar bone remodelling during orthodontic tooth movement based on an examination of changes in cathepsin K mRNA expression in parallel with the histological changes in alveolar bone.Therefore, further insights into osteoclasts differentiation and function mechanisms may provide stronger bases that will help to understand with more detail the fundaments of orthodontic tooth movement and the reaction of mechanically stressed periodontal tissues. Less