Specific microRNAs are associated with fracture healing phases, patient age and multi-trauma.

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Abstract

Immediately after a fracture occurs, a fracture hematoma (fxH) is formed. This fxH plays an important role in fracture healing and, under normal circumstances, aids in generating an environment in which a wide variety of cells orchestrate processes involved in fracture healing. MicroRNAs (miRNAs) may influence these processes. The aim of this study was therefore to determine the miRNA expression signature of human fxH in normal fracture healing and examine the potential influence of clinical parameters on these expression levels.

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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

Jacob O'Brien, Heyam Hayder, Yara Zayed … (2018)

MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.

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TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

Mengrui Wu, Guiqian Chen, YI-PING LI (2016)

Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-β and BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-β and BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-β and BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling.

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Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer

Deok-Hoon Kong, Young Kim, Mi Kim … (2018)

Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that triggers the expression of inflammatory molecules, including other cytokines and cell adhesion molecules. TNFα induces the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 was originally identified as a cell adhesion molecule that helps regulate inflammation-associated vascular adhesion and the transendothelial migration of leukocytes, such as macrophages and T cells. Recent evidence suggests that VCAM-1 is closely associated with the progression of various immunological disorders, including rheumatoid arthritis, asthma, transplant rejection, and cancer. This review covers the role and relevance of VCAM-1 in inflammation, and also highlights the emerging potential of VCAM-1 as a novel therapeutic target in immunological disorders and cancer.

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Author and article information

Journal

Journal ID (iso-abbrev): J Orthop Translat

Title: Journal of orthopaedic translation

Publisher: Elsevier BV

ISSN: 2214-031X

ISSN (Print): 2214-031X

Publication date (Electronic): Nov 2022

Volume: 37

Affiliations

[1 ] Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, the Netherlands.

[2 ] Division of Traumasurgery, Department of Surgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands.

[3 ] Department of Orthopaedic, Trauma, and Reconstructive Surgery, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.

[4 ] NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, the Netherlands.

Article

Publisher Item ID: S2214-031X(22)00064-X

DOI: 10.1016/j.jot.2022.07.002

PMC ID: 9449672

PubMed ID: 36128014

SO-VID: bd08b94d-1065-44b4-a44e-90a042ff6da2

History

Keywords: miRNA target analysis,microRNAs,Clinical parameters,Fracture healing,Gene expression

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Keywords: miRNA target analysis, microRNAs, Clinical parameters, Fracture healing, Gene expression

Specific microRNAs are associated with fracture healing phases, patient age and multi-trauma.

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Abstract

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Most cited references 39

Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer

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