Biology subjects

Willey, J. S.

Publications and source records attributed to Willey, J. S..

3 recordsLinked to original sources

bioRxiv2024

Sex-Specific Cardiovascular Adaptations to Simulated Microgravity in Sprague-Dawley Rats

Men and women have different cardiovascular responses to spaceflight; however few studies have focused on direct comparisons between sexes. Therefore, we investigated cardiovascular system differences, including arterial stiffness between socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) - an analogue for spaceflight-induced microgravity. Two weeks of HLU had no effect on body weight in either male or female rats. The index of arterial stiffness determined by ultrasound, pulse wave velocity (PWV), was greater in the aortic arch and carotid artery of females after HLU versus control females. HLU had no effect on arterial PWV in males. smooth muscle actin, myosin, collagen, elastin, and collagen-to-elastin ratio were not different in rats of either sex in response to HLU. HLU exposure did not alter individual collagen fiber characteristics in studied groups. The levels of G protein-coupled estrogen receptor (GPER) were lower in the aorta of SD females exposed to HLU compared with female controls but not in males. These changes were associated with lower PPAR {gamma} and increased oxidative stress markers (8-hydroxy-2-deoxyguanosine and p47phox) in the females. Diastolic cardiac function was altered in females after HLU versus control females. GPER agonist, G1 prevented the increase in pulse wave velocity and 8-hydroxy-2-deoxyguanosine, without altering PPAR {gamma} or p47phox. Our data revealed that lower GPER in the HLU females contributes to the development of arterial stiffness, and that the SD rat is a suitable model to study the cardiovascular response of females to HLU.

physiology↗

bioRxiv2020

Platelet TSP-1 Controls Prostate Cancer-Induced Osteoclast Differentiation and Bone Marrow-Derived Cell Mobilization through TGFβ-1

The development of distant metastasis is the main cause of prostate cancer (CaP)-related death with the skeleton being the primary site of metastasis. While the progression of primary tumors and the growth of bone metastatic tumors are well described, the mechanisms controlling pre-metastatic niche formation and homing of CaP to bone remain unclear. Through prior studies, we demonstrated that platelet secretion was required for ongoing tumor growth and pre-metastatic tumor-induce bone formation and bone marrow-derived cell mobilization to cancers supporting angiogenesis. We hypothesized that proteins released by the platelet granules were responsible for inducing changes in the pre-metastatic bone niche. We found that the classically anti-angiogenic protein thrombospondin (TSP)-1 was significantly increased in the platelets of mice bearing tumors. To determine the role of increased TSP-1, we implanted tumors in TSP-1 null animals and assessed changes in tumor growth and pre-metastatic niche formation. TSP-1 loss resulted in increased tumor size and enhanced angiogenesis but reduced bone marrow-derived cell mobilization and tumor-induced bone formation with enhanced osteoclast formation. We hypothesized that these changes in the pre-metastatic niche were due to the retention of TGF-{beta}1 in the platelets of mice with TSP-1 deleted. To assess the importance of platelet-derived TGF-{beta}1, we implanted CaP tumors in mice with platelet-specific deletion of TGF-{beta}1. Similar to TSP-1 deletion, loss of platelet TGF-{beta}1 resulted in increased angiogenesis with a milder effect on tumor size and BMDC release. Within the bone microenvironment, platelet TGF-{beta}1 deletion prevented tumor-induced bone formation due to increased osteoclastogenesis. Thus, we demonstrate that the TSP-1/TGF-{beta}1 axis regulates pre-metastatic niche formation and tumor-induced bone turnover. Targeting the platelet release of TSP-1 or TGF-{beta}1 represents a potential method to interfere with the process of CaP metastasis to bone.

cancer biology↗

bioRxiv2018

Proving Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

BackgroundLarge bone defects remain a major clinical challenge for orthopaedic surgeons. Tissue engineered bone grafts have garnered increased attention as a solution to this problem. One ideal property of any bone graft is osteoinductivity or the ability to stimulate progenitor cell differentiation into a bone forming lineage.\n\nQuestionsO_LIIs the osteoinductive potential of a porcine bone xenograft maintained in vitro after undergoing a novel decellularization and oxidation process?\nC_LIO_LIAre porcine bone scaffolds osteoinductive in an in vivo animal model?\nC_LI\n\nMethodsO_LIIn Vitro - C2C12 pre-osteoblasts were seeded on the scaffold or a commercial grade demineralized bone matrix (DBM) to study osteogenic differentiation and compare osteoinductive potential. MC3T3-E1 pre-osteoblasts were seeded on the scaffold and compared to a control monolayer to identify early markers of osteogenic differentiation.\nC_LIO_LIIn Vivo - MC3T3-E1-seeded scaffolds were implanted subcutaneously in mice and assessed for markers of early osteogenic differentiation, new bone formation (micro-computed tomography and histological assessment), and vascular infiltration (histology).\nC_LI\n\nResultsOsteoinductive potential was demonstrated in in vitro experiments by similar osteogenic marker expression compared to DBM and significantly greater expression than a control monolayer.\n\nOsteoinductivity was confirmed with in vivo experiments showing both new bone formation and vascular infiltration.\n\nConclusionPorcine bone maintains osteoinductive properties after decellularization and oxidation.\n\nClinical RelevanceThis construct could potentially serve as a bone graft substitute maintaining the osteoinductive potential of native bone. The unrestricted supply and controlled donor biology may satisfy a large clinical need for orthopaedic cases requiring bone grafting.

bioengineering↗