Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption

Lei Wang
,
Tarun Minocha
,
Bhaba K Das
ORCID logo ,
Mikaela D Kunika
,
Aarthi Kannan
,
Ling Gao
,
Subburaman Mohan
ORCID logo ,
Weirong Xing
,
Kottayil I Varughese
,
Haibo Zhao
* ORCID logo
Version 1 : Received: 30 October 2024 / Approved: 31 October 2024 / Online: 1 November 2024 (11:06:28 CET)

How to cite: Wang, L.; Minocha, T.; Das, B. K.; Kunika, M. D.; Kannan, A.; Gao, L.; Mohan, S.; Xing, W.; Varughese, K. I.; Zhao, H. FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption. Preprints 2024, 2024102584. https://doi.org/10.20944/preprints202410.2584.v1 Wang, L.; Minocha, T.; Das, B. K.; Kunika, M. D.; Kannan, A.; Gao, L.; Mohan, S.; Xing, W.; Varughese, K. I.; Zhao, H. FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption. Preprints 2024, 2024102584. https://doi.org/10.20944/preprints202410.2584.v1

Abstract

There are three FAM98 family proteins (FAM98A/B/C) in human and mice. Their physiological functions remain largely unknown. We have previously reported that Fam98a interacts with Plekhm1 in murine osteoclasts and functions in lysosome trafficking/secretion and bone resorption in osteoclasts in vitro. In this study, we found that all three Fam98 genes were expressed in precursor and mature osteoclasts. While knockdown of Fam98c by a specific short-hairpin RNA (shRNA) in osteoclast precursors attenuated osteoclastogenesis, depletion of Fam98b by a shRNA specifically disrupted osteoclast lysosome trafficking and bone resorption with phenotypes similar to Fam98a shRNA-knockdown in our previous study. Loss of Fam98a in myeloid osteoclast precursors was dispensable for trabecular and cortical bone mass in mice as well as osteoclastogenesis/bone resorption in vitro, possibly due to compensation by increased Fam98b expression in Fam98a-null osteoclasts. These findings indicate that the three Fam98 proteins play distinct roles in osteoclastogenesis and osteoclast function, respectively, that need further investigation in future studies.

Keywords

Fam98a; Fam98b; Fam98c; osteoclast; Plekhm1; lysosome; bone resorption

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.