Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.
Ushashi C DadwalCaio de Andrade StautNikhil P TewariOlatundun D AwosanyaStephen K MendenhallConner R ValuchRohit U NagarajRachel J BlosserJiliang LiIzath Nizeet AguilarPublished in: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2021)
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.
Keyphrases
- bone regeneration
- high fat diet
- mesenchymal stem cells
- high fat diet induced
- type diabetes
- endothelial cells
- bone marrow
- gene expression
- insulin resistance
- minimally invasive
- signaling pathway
- adipose tissue
- cardiovascular disease
- coronary artery bypass
- poor prognosis
- bone mineral density
- metabolic syndrome
- oxidative stress
- acute myeloid leukemia
- vascular endothelial growth factor
- glycemic control
- cell death
- soft tissue
- gestational age
- skeletal muscle
- tyrosine kinase
- blood pressure
- newly diagnosed
- electronic health record
- nk cells