The effects of high fat diet, bone healing, and BMP-2 treatment on endothelial cell growth and function

Bhatti, Fazal Ur Rehman; Dadwal, Ushashi C.; Valuch, Conner R.; Tewari, Nikhil P.; Awosanya, Olatundun D.; Staut, Caio de Andrade; Sun, Seungyup; Mendenhall, Stephen K.; Perugini, Anthony J.; Nagaraj, Rohit U.; Battina, Hanisha L.; Nazzal, Murad; Blosser, Rachel J.; Maupin, Kevin A.; Childress, Paul; Li, Jiliang; Kacena, Melissa A.

doi:10.1016/j.bone.2021.115883

Cited by 12 publications

(22 citation statements)

References 102 publications

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“…Compared to LECs, BMECs exhibited significantly more angiogenic mRNA expression differences following treatment with SRT1720. We speculate that this may occur as LECs are isolated as a homogenous CD31+ population whereas BMECs are isolated as a heterogeneous population [ 45 , 46 , 47 , 48 , 49 ] that is comprised of mature and immature EC cells, stalk and tip cells, and perhaps EC-like cells that assist in EC function [ 11 ]. Exploring and comparing the gene profiles between these subpopulations of ECs remains to be investigated but is important to better understand how drugs would impact multiple cell types.…”

Section: Discussionmentioning

confidence: 99%

“…LECs were passaged 2 times before experimental use. We have previously published on the characterization of LECs isolated in this fashion [ 49 ]. Specifically, we characterized LECs by examining Tie2 expression as evidenced in LECs isolated from mice in which tdTomato is expressed under the control of the Tie2 promoter following activation with tamoxifen and through immunocytochemical staining of CD31 as well as the functional and mRNA expression assays detailed here.…”

Section: Methodsmentioning

confidence: 99%

“…BMECs remained in this culture for seven days before being used for experiments. We have previously characterized BMECs isolated from this procedure by a number of criteria, including the examination of Tie2 expression (as evidenced in BMECs isolated from mice in which tdTomato is expressed under the control of the Tie2 promoter following activation with tamoxifen), CD31 immunocytochemical staining, and flow cytometric analysis (CD45- Ter119- CD31+ CD105+ cells) [ 47 , 48 , 49 ].…”

Section: Methodsmentioning

confidence: 99%

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The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

Dadwal

Bhatti

Awosanya

et al. 2021

IJMS

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Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20–24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

Dadwal

Bhatti

Awosanya

et al. 2021

IJMS

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“…There are many other stains for bone tissues such as Von Kossa, Gömöri trichrome, and so on, safranin O for cartilage, and endomucin for angiogenesis. 61 A list of common stains and their uses is shown in Table 3. After staining, slides are assessed using semi-automated techniques such as open-source GNU Image Manipulation Program (www.gimp.org).…”

Section: Stainingmentioning

confidence: 99%

Methodology, selection, and integration of fracture healing assessments in mice

Knox

McGuire

Natoli

et al. 2021

Journal Orthopaedic Research

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Long bone fractures are one of the most common and costly medical conditions encountered after trauma. Characterization of the biology of fracture healing and development of potential medical interventions generally involves animal models of fracture healing using varying genetic or treatment groups, then analyzing relative repair success via the synthesis of diverse assessment methodologies. Murine models are some of the most widely used given their low cost, wide variety of genetic variants, and rapid breeding and maturation. This review addresses key concerns regarding fracture repair investigations in mice and may serve as a guide in conducting and interpreting such studies. Specifically, this review details the procedures, highlights relevant parameters, and discusses special considerations for the selection and integration of the major modalities used for quantifying fracture repair in such studies, including X-ray, microcomputed tomography, histomorphometric, biomechanical, gene expression and biomarker analyses.

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“…These data suggest that treatment alone or treatment in the context of other physiological changes (spaceflight in the previous study, but T2D here) may result in important functional alterations, in ipsilateral or contralateral tibias. Therefore, although in our recent manuscript, 17 our primary goal was to examine the effects of BMP‐2 treatment for healing a femoral SBD bone healing in a high‐fat diet (HFD)‐induced T2D model, we also collected the ipsilateral and contralateral tibia for the present study.…”

Section: Introductionmentioning

confidence: 99%

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

Dadwal

Staut

Tewari

et al. 2021

Journal Orthopaedic Research

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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.

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The effects of high fat diet, bone healing, and BMP-2 treatment on endothelial cell growth and function

Cited by 12 publications

References 102 publications

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

Methodology, selection, and integration of fracture healing assessments in mice

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

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