Integrin α2β1 deficiency enhances osteogenesis via BMP-2 signaling for accelerated fracture repair.

Autor: Kronenberg D; Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University of Muenster, Muenster, Germany., Brand M; Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University of Muenster, Muenster, Germany., Everding J; Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Muenster, Muenster, Germany., Wendler L; Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University of Muenster, Muenster, Germany., Kieselhorst E; Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University of Muenster, Muenster, Germany., Timmen M; Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University of Muenster, Muenster, Germany., Hülskamp MD; Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University of Muenster, Muenster, Germany; Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Muenster, Muenster, Germany., Stange R; Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University of Muenster, Muenster, Germany. Electronic address: richard.stange@ukmuenster.de.
Jazyk: angličtina
Zdroj: Bone [Bone] 2024 Nov 03; Vol. 190, pp. 117318. Date of Electronic Publication: 2024 Nov 03.
DOI: 10.1016/j.bone.2024.117318
Abstrakt: Previous studies have shown that the absence of the collagen-binding integrin α2β1 confers protection against osteoporosis, primarily by enhancing osteoblast-mediated matrix formation, with a particular increase in collagen type I production. This study aimed to elucidate the mechanism underlying this increased matrix production. Our findings demonstrate that osteoblasts lacking integrin α2 secrete a pro-osteogenic factor that activates both TGF-β and BMP signaling pathways. Among these, BMP-2 was identified as the key signaling protein responsible for this effect, as its expression was significantly upregulated during osteoblast differentiation. Moreover, integrin α2 deficiency led to earlier and elevated BMP-2 secretion at the cell surface during osteogenesis, which promoted accelerated osteoblast differentiation. This phenomenon likely contributes to enhanced matrix production in aging animals, providing a protective effect against osteoporosis. To explore the broader implications of this phenotype, we utilized a fracture healing model. In integrin α2-deficient 12 weeks old female mice, elevated serum levels of BMP-2 were detected during the early stages of fracture repair. This upregulation of BMP signaling within the fracture callus accelerated the healing process, resulting in faster formation and mineralization of the cartilaginous callus. Additionally, the elevated BMP-2 levels facilitated earlier differentiation of chondrocytic cells, evidenced by the premature appearance of collagen type II- and type X-positive cells during endochondral ossification. Despite the accelerated healing, the overall biomechanical integrity of the repaired fractures remained uncompromised. Thus, the modulation of integrin α2β1 presents a promising therapeutic target for enhancing fracture repair by regulating BMP-2 signaling in a physiologically relevant manner.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Richard Stange reports financial support was provided by Deutsche Forschungsgemeinschaft. Michael Huelskamp reports financial support was provided by Deutsche Forschungsgemeinschaft. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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