Michael Longaker, Postdoctoral Faculty Sponsor
Circulating and extracellular vesicle-derived microRNAs as biomarkers in bone-related diseases.
Frontiers in endocrinology
2023; 14: 1168898
MicroRNAs (miRNA) are small non-coding RNA molecules that regulate posttranscriptional gene expression by repressing messengerRNA-targets. MiRNAs are abundant in many cell types and are secreted into extracellular fluids, protected from degradation by packaging in extracellular vesicles. These circulating miRNAs are easily accessible, disease-specific and sensitive to small changes, which makes them ideal biomarkers for diagnostic, prognostic, predictive or monitoring purposes. Specific miRNA signatures can be reflective of disease status and development or indicators of poor treatment response. This is especially important in malignant diseases, as the ease of accessibility of circulating miRNAs circumvents the need for invasive tissue biopsy. In osteogenesis, miRNAs can act either osteo-enhancing or osteo-repressing by targeting key transcription factors and signaling pathways. This review highlights the role of circulating and extracellular vesicle-derived miRNAs as biomarkers in bone-related diseases, with a specific focus on osteoporosis and osteosarcoma. To this end, a comprehensive literature search has been performed. The first part of the review discusses the history and biology of miRNAs, followed by a description of different types of biomarkers and an update of the current knowledge of miRNAs as biomarkers in bone related diseases. Finally, limitations of miRNAs biomarker research and future perspectives will be presented.
View details for DOI 10.3389/fendo.2023.1168898
View details for PubMedID 37293498
View details for PubMedCentralID PMC10244776
Craniofacial Dysmorphology and Impaired Suture Patterning in a Mouse Model of Frank-Ter-Haar Syndrome
LIPPINCOTT WILLIAMS & WILKINS. 2023: S89
View details for Web of Science ID 000989943300229
Standardized Quantitative Sensory Testing to assess insufficient recovery of touch discrimination in free flap surgery in extremity reconstruction.
Plastic and reconstructive surgery
BACKGROUND: With major advances in microsurgical techniques, free tissue transfer has become a widely adopted approach to treat complex soft tissue defects. However, sensory recovery is poor leaving the anaesthetic skin prone to injuries.METHODS: 28 patients with 22 anterior lateral thigh flaps and 6 latissimus dorsi flaps on their extremities participated in the study. Quantitative sensory testing and 2 points discrimination was performed in three test areas and one control on the contralateral unaffected extremity. Physical disability, mental health, quality of life and characteristics of pain were assessed by the painDetect, DASH, LEFS and sf12 questionnaires, respectively.RESULTS: Somatosensory profiles of all flaps were characterized by an overall loss of nerve function. Small-fibre function was mostly recovered while large-fibre function and thus touch discrimination was severely impaired. Mechanical detection thresholds improved over time and from periphery to the centre. Reported pain was mild to moderate and correlated with decreased physical function.CONCLUSION: Standardized Quantitative sensory testing provides a useful tool kit to assess the sensory regeneration after surgical treatment of soft tissue defects. After free tissue transfer small-fibre function recovers with nerve ingrowth in a centripetal direction from the flap margins to the centre, likely via collateral axonal sprouting from the undamaged nerves surrounding the flap. Myelinated fibres recover slowly and inefficiently.
View details for DOI 10.1097/PRS.0000000000009860
View details for PubMedID 36374559
Harnessing a Feasible and Versatile ex vivo Calvarial Suture 2-D Culture System to Study Suture Biology.
Frontiers in physiology
2022; 13: 823661
As a basic science, craniofacial research embraces multiple facets spanning from molecular regulation of craniofacial development, cell biology/signaling and ultimately translational craniofacial biology. Calvarial sutures coordinate development of the skull, and the premature fusion of one or more, leads to craniosynostosis. Animal models provide significant contributions toward craniofacial biology and clinical/surgical treatments of patients with craniofacial disorders. Studies employing mouse models are costly and time consuming for housing/breeding. Herein, we present the establishment of a calvarial suture explant 2-D culture method that has been proven to be a reliable system showing fidelity with the in vivo harvesting procedure to isolate high yields of skeletal stem/progenitor cells from small number of mice. Moreover, this method allows the opportunity to phenocopying models of craniosynostosis and in vitro tamoxifen-induction of ActincreERT2;R26Rainbow suture explants to trace clonal expansion. This versatile method tackles needs of large number of mice to perform calvarial suture research.
View details for DOI 10.3389/fphys.2022.823661
View details for PubMedID 35222087
Osteoskeletal Regenerative Ability of Exosomes Derived From Adipose-derived Stem Cells Upon Inhibition of Transforming Growth Factor-beta-signaling
ELSEVIER SCIENCE INC. 2021: E194
View details for Web of Science ID 000718306700472
The role of Wnt signaling in skin fibrosis.
Medicinal research reviews
Skin fibrosis is the excessive deposition of extracellular matrix in the dermis. Cutaneous fibrosis can occur following tissue injury, including burns, trauma, and surgery, resulting in scars that are disfiguring, limit movement and cause significant psychological distress for patients. Many molecular pathways have been implicated in the development of skin fibrosis, yet effective treatments to prevent or reverse scarring are unknown. The Wnt signaling pathways are known to play an important role in skin homeostasis, skin injury, and in the development of fibrotic skin diseases. This review provides a detailed overview of the role of the canonical Wnt signaling pathways in regulating skin scarring. We also discuss how Wnt signaling interacts with other known fibrotic molecular pathways to cause skin fibrosis. We further provide a summary of the different Wnt inhibitor types available for treating skin scarring. Understanding the role of the Wnt pathway in cutaneous fibrosis will accelerate the development of effective Wnt modulators for the treatment of skin fibrosis.
View details for DOI 10.1002/med.21853
View details for PubMedID 34431110
An Evolutionary Conserved Signaling Network Between Mouse and Human Underlies the Differential Osteoskeletal Potential of Frontal and Parietal Calvarial Bones.
Frontiers in physiology
2021; 12: 747091
The mammalian calvarial vault is an ancient and highly conserved structure among species, however, the mechanisms governing osteogenesis of the calvarial vault and how they might be conserved across mammalian species remain unclear. The aim of this study was to determine if regional differences in osteogenic potential of the calvarial vault, first described in mice, extend to humans. We derived human frontal and parietal osteoblasts from fetal calvarial tissue, demonstrating enhanced osteogenic potential both in vitro and in vivo of human frontal derived osteoblasts compared to parietal derived osteoblasts. Furthermore, we found shared differential signaling patterns in the canonical WNT, TGF-beta, BMP, and FGF pathways previously described in the mouse to govern these regional differences in osteogenic potential. Taken together, our findings unveil evolutionary conserved similarities both at functional and molecular level between the mouse and human calvarial bones, providing further support that studies employing mouse models, are suitable for translational studies to human.
View details for DOI 10.3389/fphys.2021.747091
View details for PubMedID 34744787
Exosomes - a tool for bone tissue engineering.
Tissue engineering. Part B, Reviews
Mesenchymal stem cells (MSC) have been repeatedly shown to be a valuable source for cell-based therapy in regenerative medicine, including bony tissue repair. However, engraftment at the injury site is poor. Recently, it has been suggested that MSCs and other cells act via a paracrine signaling mechanism. Exosomes are nanostructures that have been implicated in this process. They carry DNA, RNA, proteins and lipids and play an important role in cell-to-cell communication directly modulating their target cell at a transcriptional level. In a bone microenvironment, they have been shown to increase osteogenesis and osteogenic differentiation in vivo and in vitro. In the following review, we will discuss the most advanced and significant knowledge of biological functions of exosomes in bone regeneration and their clinical applications in osseous diseases.
View details for DOI 10.1089/ten.TEB.2020.0246
View details for PubMedID 33297857