Publications by authors named "W David Hill"

1,237 Publications

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Characterization of Differentially Expressed miRNAs by CXCL12/SDF-1 in Human Bone Marrow Stromal Cells.

Biomol Concepts 2021 Oct 13;12(1):132-143. Epub 2021 Oct 13.

Department of Orthopedics, Augusta University, Augusta, GA.

Stromal cell-derived factor 1 (SDF-1) is known to influence bone marrow stromal cell (BMSC) migration, osteogenic differentiation, and fracture healing. We hypothesize that SDF-1 mediates some of its effects on BMSCs through epigenetic regulation, specifically via microRNAs (miRNAs). MiRNAs are small non-coding RNAs that target specific mRNA and prevent their translation. We performed global miRNA analysis and determined several miRNAs were differentially expressed in response to SDF-1 treatment. Gene Expression Omnibus (GEO) dataset analysis showed that these miRNAs play an important role in osteogenic differentiation and fracture healing. KEGG and GO analysis indicated that SDF-1 dependent miRNAs changes affect multiple cellular pathways, including fatty acid biosynthesis, thyroid hormone signaling, and mucin-type O-glycan biosynthesis pathways. Furthermore, bioinformatics analysis showed several miRNAs target genes related to stem cell migration and differentiation. This study's findings indicated that SDF-1 induces some of its effects on BMSCs function through miRNA regulation.
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http://dx.doi.org/10.1515/bmc-2021-0015DOI Listing
October 2021

Tryptophan-Kynurenine Pathway in COVID-19-Dependent Musculoskeletal Pathology: A Minireview.

Mediators Inflamm 2021 5;2021:2911578. Epub 2021 Oct 5.

Department of Cell Biology and Anatomy, Augusta University, Augusta, GA, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), affecting multiple organ systems, including the respiratory tract and lungs. Several studies have reported that the tryptophan-kynurenine pathway is altered in COVID-19 patients. The tryptophan-kynurenine pathway plays a vital role in regulating inflammation, metabolism, immune responses, and musculoskeletal system biology. In this minireview, we surmise the effects of the kynurenine pathway in COVID-19 patients and how this pathway might impact muscle and bone biology.
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http://dx.doi.org/10.1155/2021/2911578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492288PMC
October 2021

Characteristics of phantom limb pain in U.S. civilians and service members.

Scand J Pain 2021 Sep 17. Epub 2021 Sep 17.

Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Objectives: The population of Americans with limb loss is on the rise, with a different profile than in previous generations (e.g., greater incidence of amputation due to diabetes). This study aimed to identify the key characteristics of phantom limb sensation (PLS) and pain (PLP) in a current sample of Americans with limb loss.

Methods: This cross-sectional study is the first large-scale (n=649) study on PLP in the current population of Americans with limb loss. A convenience sample of military and civilian persons missing one or more major limbs was surveyed regarding their health history and experience with phantom limb phenomena.

Results: Of the participants surveyed, 87% experienced PLS and 82% experienced PLP. PLS and PLP typically first occurred immediately after amputation (47% of cases), but for a small percentage (3-4%) onset did not occur until over a year after amputation. Recent PLP severity decreased over time (β=0.028, 95% CI: -0.05-0.11), but most participants reported PLP even 10 years after amputation. Higher levels of recent PLP were associated with telescoping (β=0.123, 95% CI: 0.04-0.21) and higher levels of pre-amputation pain (β=0.104, 95% CI: 0.03-0.18). Those with congenitally missing limbs experienced lower levels of recent PLP (t (37.93)=3.93, p<0.01) but there were no consistent differences in PLP between other amputation etiologies.

Conclusions: Phantom limb phenomena are common and enduring. Telescoping and pre-amputation pain are associated with higher PLP. Persons with congenitally missing limbs experience lower levels of PLP than those with amputation(s), yet PLP is common even in this subpopulation.
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http://dx.doi.org/10.1515/sjpain-2021-0139DOI Listing
September 2021

Age-associated changes in microRNAs affect the differentiation potential of human mesenchymal stem cells: Novel role of miR-29b-1-5p expression.

Bone 2021 Dec 14;153:116154. Epub 2021 Aug 14.

Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29403, United States of America; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403, United States of America; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Center for Healthy Aging, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America. Electronic address:

Age-associated osteoporosis is widely accepted as involving the disruption of osteogenic stem cell populations and their functioning. Maintenance of the local bone marrow (BM) microenvironment is critical for regulating proliferation and differentiation of the multipotent BM mesenchymal stromal/stem cell (BMSC) population with age. The potential role of microRNAs (miRNAs) in modulating BMSCs and the BM microenvironment has recently gained attention. However, miRNAs expressed in rapidly isolated BMSCs that are naïve to the non-physiologic standard tissue culture conditions and reflect a more accurate in vivo profile have not yet been reported. Here we directly isolated CD271 positive (+) BMSCs within hours from human surgical BM aspirates without culturing and performed microarray analysis to identify the age-associated changes in BMSC miRNA expression. One hundred and two miRNAs showed differential expression with aging. Target prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the up-regulated miRNAs targeting genes in bone development pathways were considerably enriched. Among the differentially up-regulated miRNAs the novel passenger strand miR-29b-1-5p was abundantly expressed as a mature functional miRNA with aging. This suggests a critical arm-switching mechanism regulates the expression of the miR-29b-1-5p/3p pair shifting the normally degraded arm, miR-29b-1-5p, to be the dominantly expressed miRNA of the pair in aging. The normal guide strand miR-29b-1-3p is known to act as a pro-osteogenic miRNA. On the other hand, overexpression of the passenger strand miR-29b-1-5p in culture-expanded CD271+ BMSCs significantly down-regulated the expression of stromal cell-derived factor 1 (CXCL12)/ C-X-C chemokine receptor type 4 (SDF-1(CXCL12)/CXCR4) axis and other osteogenic genes including bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (RUNX2). In contrast, blocking of miR-29b-1-5p function using an antagomir inhibitor up-regulated expression of BMP-2 and RUNX2 genes. Functional assays confirmed that miR-29b-1-5p negatively regulates BMSC osteogenesis in vitro. These novel findings provide evidence of a pathogenic anti-osteogenic role for miR-29b-1-5p and other miRNAs in age-related defects in osteogenesis and bone regeneration.
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http://dx.doi.org/10.1016/j.bone.2021.116154DOI Listing
December 2021

Capturing cancer evolution using genetically engineered mouse models (GEMMs).

Trends Cell Biol 2021 Aug 13. Epub 2021 Aug 13.

Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; University College London Hospitals NHS Trust, London, UK. Electronic address:

Initiating from a single cell, cancer undergoes clonal evolution, leading to a high degree of intratumor heterogeneity (ITH). The arising genetic heterogeneity between cancer cells is influenced by exogenous and endogenous forces that shape the composition of clones within tumors. Preclinical mouse models have provided a valuable tool for understanding cancer, helping to build a fundamental understanding of tumor initiation, progression, and metastasis. Until recently, genetically engineered mouse models (GEMMS) of cancer had lacked the genetic diversity found in human tumors, in which evolution may be driven by long-term carcinogen exposure and DNA damage. However, advances in sequencing technology and in our understanding of the drivers of genetic instability have given us the knowledge to generate new mouse models, offering an approach to functionally explore mechanisms of tumor evolution.
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http://dx.doi.org/10.1016/j.tcb.2021.07.003DOI Listing
August 2021
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