Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Novel Mechanism for Bone Loss: Platelet Count Negatively Correlates with Bone Mineral Density via Megakaryocyte-Derived RANKL

Shohei Kikuchi
† ,
Akinori Wada
† ORCID logo ,
Yusuke Kamihara
,
Imari Yamamoto
,
Daiki Kirigaya
,
Kohei Kunimoto
,
Ryusuke Horaguchi
,
Takuma Fujihira
,
Yoshimi Nabe
,
Tomoki Minemura
,
Nam H Dang
,
Tsutomu Sato
*
†
These authors contributed equally to this work.
Version 1 : Received: 5 July 2023 / Approved: 5 July 2023 / Online: 5 July 2023 (10:51:58 CEST)

A peer-reviewed article of this Preprint also exists.

Kikuchi, S.; Wada, A.; Kamihara, Y.; Yamamoto, I.; Kirigaya, D.; Kunimoto, K.; Horaguchi, R.; Fujihira, T.; Nabe, Y.; Minemura, T.; Dang, N.H.; Sato, T. A Novel Mechanism for Bone Loss: Platelet Count Negatively Correlates with Bone Mineral Density via Megakaryocyte-Derived RANKL. Int. J. Mol. Sci. 2023, 24, 12150. Kikuchi, S.; Wada, A.; Kamihara, Y.; Yamamoto, I.; Kirigaya, D.; Kunimoto, K.; Horaguchi, R.; Fujihira, T.; Nabe, Y.; Minemura, T.; Dang, N.H.; Sato, T. A Novel Mechanism for Bone Loss: Platelet Count Negatively Correlates with Bone Mineral Density via Megakaryocyte-Derived RANKL. Int. J. Mol. Sci. 2023, 24, 12150.

Abstract

A potential association between hematopoietic stem cell status in the bone marrow and the surrounding bone tissue has been hypothesized, and some studies have investigated the link between blood count and bone mineral density (BMD), although their exact relationship remains controversial. Moreover, biological factors linking the two are largely unknown. In our present study, we found no clear association between platelet count and BMD in the female group, with aging having a very strong effect on BMD. On the other hand, a significant negative correlation was found between platelet count and BMD in the male group. As a potential mechanism, we examined whether megakaryocytes, the source of platelet production, secrete cytokines that regulate BMD, namely OPG, M-CSF, and RANKL. We detected the production of these cytokines by megakaryocytes deriving from bone marrow mononuclear cells and found that RANKL was negatively correlated with BMD. This finding suggests that RANKL production by megakaryocytes may mediate the negative correlation between platelet count and BMD. To our knowledge, this is the first report to analyze bone marrow cells as a mechanism for the association between blood count and BMD. Our study may provide new insights into the development and potential treatment of osteoporosis.

Keywords

platelet; bone mineral density; megakaryocyte; RANKL

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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.

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