Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.

Autor: Dadwal UC; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indiana, USA.; VA Research Service, Richard L. Roudebush VA Medical Center, Indiana, USA., Staut CA; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indiana, USA., Tewari NP; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indiana, USA., Awosanya OD; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indiana, USA., Mendenhall SK; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indiana, USA., Valuch CR; Department of Biology, Indiana University Purdue University Indianapolis, Indiana, USA., Nagaraj RU; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indiana, USA., Blosser RJ; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indiana, USA.; VA Research Service, Richard L. Roudebush VA Medical Center, Indiana, USA., Li J; Department of Biology, Indiana University Purdue University Indianapolis, Indiana, USA., Kacena MA; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indiana, USA.; VA Research Service, Richard L. Roudebush VA Medical Center, Indiana, USA.
Jazyk: angličtina
Zdroj: Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2022 Feb; Vol. 40 (2), pp. 439-448. Date of Electronic Publication: 2021 Mar 26.
DOI: 10.1002/jor.25033
Abstrakt: Type 2 diabetes (T2D) results in physiological and structural changes in bone, contributing to poor fracture healing. T2D compromises microvascular performance, which can negatively impact bone regeneration as angiogenesis is required for new bone formation. We examined the effects of bone morphogenetic protein-2 (BMP-2) administered locally at the time of femoral segmental bone defect (SBD) surgery, and its angiogenic impacts on endothelial cells (ECs) isolated from the ipsilateral or contralateral tibia in T2D mice. Male C57BL/6 mice were fed either a low-fat diet (LFD) or high-fat diet (HFD) starting at 8 weeks. After 12 weeks, the T2D phenotype in HFD mice was confirmed via glucose and insulin tolerance testing and echoMRI, and all mice underwent SBD surgery. Mice were treated with BMP-2 (5 µg) or saline at the time of surgery. Three weeks postsurgery, bone marrow ECs were isolated from ipsilateral and contralateral tibias, and proliferation, angiogenic potential, and gene expression of the cells was analyzed. BMP-2 treatment increased EC proliferation by two fold compared with saline in LFD contralateral tibia ECs, but no changes were seen in surgical tibia EC proliferation. BMP-2 treatment enhanced vessel-like structure formation in HFD mice whereas, the opposite was observed in LFD mice. Still, in BMP-2 treated LFD mice, ipsilateral tibia ECs increased expression of CD31, FLT-1, ANGPT1, and ANGPT2. These data suggest that the modulating effects of T2D and BMP-2 on the microenvironment of bone marrow ECs may differentially influence angiogenic properties at the fractured limb versus the contralateral limb.
(© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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