Intracellular membrane trafficking in bone resorbing osteoclasts
Article first published online: 18 JUL 2003
Copyright © 2003 Wiley-Liss, Inc.
Microscopy Research and Technique
Special Issue: Osteoclast Biology
Volume 61, Issue 6, pages 496–503, 15 August 2003
How to Cite
Mulari, M., Vääräniemi, J. and Väänänen, H. K. (2003), Intracellular membrane trafficking in bone resorbing osteoclasts. Microsc. Res. Tech., 61: 496–503. doi: 10.1002/jemt.10371
- Issue published online: 18 JUL 2003
- Article first published online: 18 JUL 2003
- Manuscript Accepted: 11 FEB 2003
- Manuscript Received: 21 NOV 2002
There is ample evidence now that the two major events in bone resorption, namely dissolution of hydroxyapatite and degradation of the organic matrix, are performed by osteoclasts. The resorption cycle involves several specific cellular activities, where intracellular vesicular trafficking plays a crucial role. Although details of these processes started to open up only recently, it is clear that vesicular trafficking is needed in several specific steps of osteoclast functioning. Several plasma membrane domains are formed during the polarization of the resorbing cells. Multinucleated osteoclasts create a tight sealing to the extracellular matrix as a first indicator of their resorption activity. Initial steps of the sealing zone formation are αvβ3-integrin mediated, but the final molecular interaction(s) between the plasma membrane and mineralized bone matrix is still unknown. A large number of acidic intracellular vesicles then fuse with the bone-facing plasma membrane to form a ruffled border membrane, which is the actual resorbing organelle. The formation of a ruffled border is regulated by a small GTP-binding protein, rab7, which indicates the late endosomal character of the ruffled border membrane. Details of specific membrane transport processes in the osteoclasts, e.g., the formation of the sealing zone and transcytosis of bone degradation products from the resorption lacuna to the functional secretory domain remain to be clarified. It is tempting to speculate that specific features of vesicular trafficking may offer several potential new targets for drug therapy of bone diseases. Microsc. Res. Tech. 61:496–503, 2003. © 2003 Wiley-Liss, Inc.