Cellular and Molecular Life Sciences

, Volume 76, Issue 7, pp 1243–1253 | Cite as

Coupling factors involved in preserving bone balance

  • Beom-Jun Kim
  • Jung-Min KohEmail author


Coupling during bone remodeling refers to the spatial and temporal coordination of bone resorption with bone formation. Studies have assessed the subtle interactions between osteoclasts and osteoblasts to preserve bone balance. Traditionally, coupling research related to osteoclast function has focused on bone resorption activity causing the release of growth factors embedded in the bone matrix. However, considerable evidence from in vitro, animal, and human studies indicates the importance of the osteoclasts themselves in coupling phenomena, and many osteoclast-derived coupling factors have been identified. These include sphingosine-1-phosphate, vesicular–receptor activator of nuclear factor-κB, collagen triple helix repeat containing 1, and cardiotrophin-1. Interestingly, neuronal guidance molecules, such as slit guidance ligand 3, semaphorin (SEMA) 3A, SEMA4D, and netrin-1, originally identified as instructive cues allowing the navigation of growing axons to their targets, have been shown to be involved in the intercellular cross-talk among bone cells. This review discusses osteoclast–osteoblast coupling signals, including recent advances and the potential roles of these signals as therapeutic targets for osteoporosis and as biomarkers predicting human bone health.


Bone remodeling Coupling factor Axon guidance molecule Therapeutic target Biomarker 



The authors would like to thank Mark W. Hamrick at the Medical College of Georgia, Augusta University (Augusta, GA, USA) for his helpful comments. This study was supported by grants from the Bio & Medical Technology Development Program of the National Research Foundation, funded by the Korean government, MSIP (project no. 2016M3A9E8941329), and from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (project nos. HI15C2792 and HI15C0377).

Author contributions

BK and JK summarized the literature and wrote the paper. Both authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have patents on S1P as a biomarker and SLIT3 as a therapeutic target for osteoporosis.


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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Division of Endocrinology and Metabolism, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea

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