REVIEW article
Front. Cell Dev. Biol.
Sec. Signaling
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1670716
This article is part of the Research TopicOsteocytes in Bone Health and BeyondView all 5 articles
Osteocytes: Master Orchestrators of Skeletal Homeostasis, Remodeling, and Osteoporosis Pathogenesis
Provisionally accepted
- 1The First Affiliated Hospital of Shandong First Medical University, Jinan, China
- 2Orthopaedic and Rehabilitation, Yale School of Medicine, Department of Comparative Medicine, New Haven, United States
- 3Shandong University of Traditional Chinese Medicine, Jinan, China
- 4The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,, Jinan, China
- 5The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The skeleton functions as an endocrine organ. Osteocytes maintenance of skeletal strength and energy balance by sensing mechanical stress and communicating with surrounding cells. They are currently considered key regulators of bone remodeling, mineral metabolism, and systemic homeostasis. Osteocytes originate from osteoblasts and are embedded in the lacunar-tubular network. They express proteins such as DMP1, sclerostin, and FGF23, and influence Wnt signaling, the RANKL/OPG axis, and phosphate metabolism. We review the latest studies in the field of osteocyte biology, focusing on their mechanotransduction through Piezo1 and integrins, regulation of osteoclastogenesis and osteogenesis, and their interactions with the bone marrow microenvironment, including immune and vascular cells. In osteoporosis, osteocyte dysfunction is manifested by apoptosis, ferroptosis, and pyroptosis. These changes, together with altered secretion, lead to uncoupled remodeling, disruption of the lacuno-canalicular network (LCN), and metabolic imbalances that are intertwined with inflammation and bone marrow fat deposition. Osteocytes play an important role in fracture healing and adaptive remodeling under mechanical stimulation, promoting angiogenesis and stem cell recruitment. A growing number of emerging approaches, including stem cell therapy, CRISPR editing, and AI-driven multi-omics for precision medicine, are accelerating osteocyte-related research and the development of therapeutic strategies. These studies reveal the clinical potential of osteocyte-targeted therapies to prevent osteoporosis, improve bone strength, and enhance regeneration. By integrating molecular, cellular, and systems knowledge, we highlight osteocytes as a key therapeutic target to combat bone diseases and promote bone regeneration.
Keywords: Osteocyte, Osteoporosis, Bone, Microenviroment, Fracture
Received: 22 Jul 2025; Accepted: 09 Sep 2025.
Copyright: © 2025 Wu, Gan, Liu, Qiu, Tan, Xu and Haipeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Donghao Gan, Orthopaedic and Rehabilitation, Yale School of Medicine, Department of Comparative Medicine, New Haven, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.