%0 Journal Article
%T Osteoclast-derived coupling factors: origins and state-of-play Louis V Avioli Lecture, ASBMR 2023.
%A Sims NA
%J J Bone Miner Res
%V 0
%N 0
%D 2024 Jul 11
%M 38990205
%F 6.39
%R 10.1093/jbmr/zjae110
%X Coupling, the mechanism that controls the sequence of events in bone remodelling, is a fundamental theory for understanding the way the skeleton changes throughout life. This review is an adapted version of the Louis V Avioli lecture, delivered at the Annual Scientific Meeting of the American Society of Bone and Mineral Research. It outlines the history of the coupling concept and details how coupling occurs within trabecular and cortical bone and describes its multiple contexts and the many mechanisms suggested to couple bone forming osteoblasts to the prior action of osteoclasts on the same bone surface. These mechanisms include signals produced at each stage of the remodelling sequence (resorption, reversal, and formation), such as factors released by osteoclasts through their resorptive action and through protein synthesis, molecules deposited in the cement line during the reversal phase, and potentially signals from osteocytes within the local bone environment. The review highlights two examples of coupling factors (Cardiotrophin 1 and EphrinB2:EphB4) to illustrate the limited data available, and the need to integrate both the many functions of these factors within the basic multicellular unit (BMU), and the multiple origins of these factors, including other cell types present during the remodelling sequence (such as osteocytes, macrophages, endothelial cells, and T-cells).<BR>Coupling is a fundamental process by which bone resorbing cells (osteoclasts) are followed by bone forming cells (osteoblasts) on the same surface during the process of bone remodelling. This review outlines the history, basic concepts, and mechanisms proposed, and suggests directions for further research into the way this sequence of events in controlled in bone maintenance, development, and healing.