NDLI: Activated FGFR3 suppresses bone regeneration and bone mineralization in an ovariectomized mouse model

Content Provider	Springer Nature : BioMed Central
Author	Kawashima, Itaru Matsushita, Masaki Mishima, Kenichi Kamiya, Yasunari Osawa, Yusuke Ohkawara, Bisei Ohno, Kinji Kitoh, Hiroshi Imagama, Shiro
Abstract	Background Postmenopausal osteoporosis is a widespread health concern due to its prevalence among older adults and an associated high risk of fracture. The downregulation of bone regeneration delays fracture healing. Activated fibroblast growth factor receptor 3 (FGFR3) accelerates bone regeneration at juvenile age and downregulates bone mineralization at all ages. However, the impact of FGFR3 signaling on bone regeneration and bone mineralization post-menopause is still unknown. This study aimed to evaluate the impact of FGFR3 signaling on bone regeneration and bone mineralization during menopause by developing a distraction osteogenesis (DO) mouse model after ovariectomy (OVX) using transgenic mice with activated FGFR3 driven by Col2a1 promoter (Fgfr3 mice). Methods The OVX or sham operations were performed in 8-week-old female Fgfr3 and wild-type mice. After 8 weeks of OVX surgery, DO surgery in the lower limb was performed. The 5-day-latency period followed by performing distraction for 9 days. Bone mineral density (BMD) and bone regeneration was assessed by micro-computed tomography (micro-CT) scan and soft X-ray. Bone volume in the distraction area was also evaluated by histological analysis after 7 days at the end of distraction. Osteogenic differentiation and mineralization of bone marrow-derived mesenchymal stem cells (BMSCs) derived from each mouse after 8 weeks of the OVX or sham operations were also evaluated with and without an inhibitor for FGFR3 signaling (meclozine). Results BMD decreased after OVX in both groups, and it further deteriorated in Fgfr3 mice. Poor callus formation after DO was also observed in both groups with OVX, and the amount of regenerated bone was further decreased in Fgfr3 mice. Similarly, histological analysis revealed that Fgfr3 OVX mice showed lower bone volume. Osteogenic differentiation and mineralization of BMSCs were also deteriorated in Fgfr3 OVX mice. An inhibitor for FGFR3 signaling dramatically reversed the inhibitory effect of OVX and FGFR3 signaling on BMSC mineralization. Conclusion Upregulated FGFR3 decreased newly regenerated bone after DO and BMD in OVX mice. FGFR3 signaling can be a potential therapeutic target in patients with postmenopausal osteoporosis.
Related Links	https://bmcmusculoskeletdisord.biomedcentral.com/counter/pdf/10.1186/s12891-023-06318-9.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14712474
DOI	10.1186/s12891-023-06318-9
Journal	BMC Musculoskeletal Disorders
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2023-03-16
Access Restriction	Open
Subject Keyword	Orthopedics Rehabilitation Rheumatology Sports Medicine Internal Medicine Epidemiology Postmenopausal osteoporosis Fibroblast growth factor receptors 3 FGFR3 Distraction osteogenesis Ovariectomy Meclozine
Content Type	Text
Resource Type	Article
Subject	Orthopedics and Sports Medicine Rheumatology
Journal Impact Factor	2.2/2023
5-Year Journal Impact Factor	2.6/2023

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