<em>Fgfr1</em> deficiency in osteocytes leads to increased bone mass by enhancing Wnt/β-catenin signaling

Tang, Yubin<sup>1,2,*</sup>; Yang, Peng<sup>1,*</sup>; Jin, Min<sup>1,*</sup>; Huang, Shuo<sup>1</sup>; Chen, Hangang<sup>1</sup>; Chen, Lin<sup>1</sup>; Yang, Jing<sup>1</sup>; Su, Nan<sup>1</sup>

Affiliations

¹Center of Bone Metabolism and Repair, Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, PR China

²Emergency Department of the 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, Gansu, PR China

Abstract and keywords

Osteoporosis (OP) is the most common skeletal disease in middle-aged and elderly people. A comprehensive understanding of the pathogenesis of osteoporosis is important. Fibroblast growth factor receptor 1 (FGFR1) is an important molecule for skeletal development and bone remodeling. Osteocytes are the most numerous cells in bone and play critical roles in bone homeostasis, however the effect of FGFR1 on osteocytes is still unclear. To clarify the direct effects of FGFR1 on osteocytes, we conditionally deleted Fgfr1 in osteocytes with Dentin matrix protein 1 (Dmp1)-Cre. We found that mice lacking Fgfr1 in osteocytes (Fgfr1^f/f;Dmp-cre, MUT) showed increased trabecular bone mass at 2 and 6 months of age, which resulted from enhanced bone formation and decreased bone resorption. Furthermore, the cortical bone was thicker in WT mice than that in MUT mice at 2 and 6 months of age. Histological analysis showed that MUT mice had a decreased number of osteocytes but an increased number of osteocyte dendrites. We further found that mice lacking Fgfr1 in osteocytes showed enhanced activation of β-catenin signaling. The expression of sclerostin, an inhibitor of Wnt/β-catenin signaling, was obviously decreased in MUT mice. Furthermore, we found that FGFR1 can inhibit the expression of β-catenin and decrease the activity of β-catenin signaling. In brief, our study showed that FGFR1 in osteocytes can regulate bone mass by regulating Wnt/β-catenin signaling, providing genetic evidence that FGFR1 plays essential roles in osteocytes during bone remodeling and suggesting that FGFR1 is a potential therapeutic target for the prevention of bone loss.

Keywords: FGFR1; Osteocyte; Bone remodeling; Wnt/β-catenin; Sclerostin

Links

DOI: 10.1016/j.bone.2023.116817

PubMed: 37268269

WoS: 001023804900001

History

Received: 2023-01-3

Revised: 2023-05-23

Accepted: 2023-05-26

Online: 2023-06-1

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