Identification of the miRNAome in human fracture callus and nonunion tissues
Background: Nonunions remain a challenging post-traumatic complication that often leads to a financial and health burden that affects the patient's quality of life. Despite a wealth of knowledge about fracture repair, especially gene and more recently miRNA expression, much remains unknown abou...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Journal of Orthopaedic Translation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X23000104 |
| _version_ | 1797837095090257920 |
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| author | Michael Hadjiargyrou Leonidas Salichos Peter Kloen |
| author_facet | Michael Hadjiargyrou Leonidas Salichos Peter Kloen |
| author_sort | Michael Hadjiargyrou |
| collection | DOAJ |
| description | Background: Nonunions remain a challenging post-traumatic complication that often leads to a financial and health burden that affects the patient's quality of life. Despite a wealth of knowledge about fracture repair, especially gene and more recently miRNA expression, much remains unknown about the molecular differences between normal physiological repair (callus tissue) and a nonunion. To probe this lack of knowledge, we embarked on a study that sought to identify and compare the human miRNAome of normal bone to that present in a normal fracture callus and those from two different classic nonunion types, hypertrophic and oligotrophic. Methods: Normal bone and callus tissue samples were harvested during revision surgery from patients with physiological fracture repair and nonunions (hypertrophic and oligotrophic) and analyzed using histology. Also, miRNAs were isolated and screened using microarrays followed by bioinformatic analyses, including, differential expression, pathways and biological processes, as well as elucidation of target genes. Results: Out of 30,424 mature miRNAs (from 203 organisms) screened via microarrays, 635 (∼2.1%) miRNAs were found to be upregulated and 855 (∼2.8%) downregulated in the fracture callus and nonunion tissues as compared to intact bone. As our tissue samples were derived from humans, we focused on the human miRNAs and out of the 4223 human miRNAs, 86 miRNAs (∼2.0%) were upregulated and 51 (∼1.2%) were downregulated. Although there were similarities between the three experimental samples, we also found specific miRNAs that were unique to individual samples. We further identified the predicted target genes from these differentially expressed miRNAs as well as the relevant biological processes, including specific signaling pathways that are activated in all three experimental samples. Conclusion: Collectively, this is the first comprehensive study reporting on the miRNAome of intact bone as compared to fracture callus and nonunion tissues. Further, we identify specific miRNAs involved in normal physiological fracture repair as well as those of nonunions. The translational potential of this article: The data generated from this study further increase our molecular understanding of the roles of miRNAs during normal and aberrant fracture repair and this knowledge can be used in the future in the development of miRNA-based therapeutics for skeletal regeneration. |
| first_indexed | 2024-04-09T15:20:22Z |
| format | Article |
| id | doaj.art-60b6e37776964d9da6b52895f2a214a2 |
| institution | Directory Open Access Journal |
| issn | 2214-031X |
| language | English |
| last_indexed | 2024-04-09T15:20:22Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Orthopaedic Translation |
| spelling | doaj.art-60b6e37776964d9da6b52895f2a214a22023-04-29T14:49:47ZengElsevierJournal of Orthopaedic Translation2214-031X2023-03-0139113123Identification of the miRNAome in human fracture callus and nonunion tissuesMichael Hadjiargyrou0Leonidas Salichos1Peter Kloen2Department of Biological & Chemical Sciences, New York Institute of Technology, Old Westbury, NY, 11568, USA; Corresponding author.Department of Biological & Chemical Sciences, New York Institute of Technology, Old Westbury, NY, 11568, USADepartment of Orthopedic Surgery and Sports Medicine, Amsterdam UMC Location Meibergdreef, Amsterdam, the Netherlands; Amsterdam Movement Sciences, (Tissue Function and Regeneration), Amsterdam, the NetherlandsBackground: Nonunions remain a challenging post-traumatic complication that often leads to a financial and health burden that affects the patient's quality of life. Despite a wealth of knowledge about fracture repair, especially gene and more recently miRNA expression, much remains unknown about the molecular differences between normal physiological repair (callus tissue) and a nonunion. To probe this lack of knowledge, we embarked on a study that sought to identify and compare the human miRNAome of normal bone to that present in a normal fracture callus and those from two different classic nonunion types, hypertrophic and oligotrophic. Methods: Normal bone and callus tissue samples were harvested during revision surgery from patients with physiological fracture repair and nonunions (hypertrophic and oligotrophic) and analyzed using histology. Also, miRNAs were isolated and screened using microarrays followed by bioinformatic analyses, including, differential expression, pathways and biological processes, as well as elucidation of target genes. Results: Out of 30,424 mature miRNAs (from 203 organisms) screened via microarrays, 635 (∼2.1%) miRNAs were found to be upregulated and 855 (∼2.8%) downregulated in the fracture callus and nonunion tissues as compared to intact bone. As our tissue samples were derived from humans, we focused on the human miRNAs and out of the 4223 human miRNAs, 86 miRNAs (∼2.0%) were upregulated and 51 (∼1.2%) were downregulated. Although there were similarities between the three experimental samples, we also found specific miRNAs that were unique to individual samples. We further identified the predicted target genes from these differentially expressed miRNAs as well as the relevant biological processes, including specific signaling pathways that are activated in all three experimental samples. Conclusion: Collectively, this is the first comprehensive study reporting on the miRNAome of intact bone as compared to fracture callus and nonunion tissues. Further, we identify specific miRNAs involved in normal physiological fracture repair as well as those of nonunions. The translational potential of this article: The data generated from this study further increase our molecular understanding of the roles of miRNAs during normal and aberrant fracture repair and this knowledge can be used in the future in the development of miRNA-based therapeutics for skeletal regeneration.http://www.sciencedirect.com/science/article/pii/S2214031X23000104microRNAmiRNANonunionFractureCallusHypertrophic |
| spellingShingle | Michael Hadjiargyrou Leonidas Salichos Peter Kloen Identification of the miRNAome in human fracture callus and nonunion tissues Journal of Orthopaedic Translation microRNA miRNA Nonunion Fracture Callus Hypertrophic |
| title | Identification of the miRNAome in human fracture callus and nonunion tissues |
| title_full | Identification of the miRNAome in human fracture callus and nonunion tissues |
| title_fullStr | Identification of the miRNAome in human fracture callus and nonunion tissues |
| title_full_unstemmed | Identification of the miRNAome in human fracture callus and nonunion tissues |
| title_short | Identification of the miRNAome in human fracture callus and nonunion tissues |
| title_sort | identification of the mirnaome in human fracture callus and nonunion tissues |
| topic | microRNA miRNA Nonunion Fracture Callus Hypertrophic |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X23000104 |
| work_keys_str_mv | AT michaelhadjiargyrou identificationofthemirnaomeinhumanfracturecallusandnonuniontissues AT leonidassalichos identificationofthemirnaomeinhumanfracturecallusandnonuniontissues AT peterkloen identificationofthemirnaomeinhumanfracturecallusandnonuniontissues |