Brian O'Callaghan Diekman

Works (20)

Updated: April 6th, 2024 05:01

2024 article

DNA Damage and Cellular Senescence in Osteoarthritis: An Unexpected Role for Interferon Regulatory Factor 1 in Chondrocyte DNA Repair

Diekman, B. O., & Loeser, R. F. (2024, February 27). ARTHRITIS & RHEUMATOLOGY.

By: B. Diekman n & R. Loeser *

Source: Web Of Science
Added: April 1, 2024

2023 review

Epigenetics as a mediator of genetic risk in osteoarthritis: role during development, homeostasis, aging, and disease progression

[Review of ]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 324(5), C1078–C1088.

By: D. Richard *, T. Capellini * & B. Diekman n

author keywords: epigenetics; genetics; GWAS; osteoarthritis
MeSH headings : Adult; Humans; Genetic Predisposition to Disease / genetics; Genome-Wide Association Study; Epigenesis, Genetic / genetics; Aging / genetics; Homeostasis / genetics; Osteoarthritis / genetics; Risk Factors; Disease Progression
TL;DR: Examples of how epigenetic shifts at distinct life stages can alter the risk for OA are provided and it is proposed that massively parallel reporter assays (MPRAs) will be a valuable tool to test the function of putative OA GWAS variants in chondrocytes from different life stages. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: June 12, 2023

2023 journal article

Patient-derived extracellular matrix demonstrates role of COL3A1 in blood vessel mechanics

ACTA BIOMATERIALIA, 166, 346–359.

By: E. Doherty  n, W. Aw n, E. Warren  n, M. Hockenberry *, C. Whitworth *, G. Krohn  n, S. Howell *, B. Diekman n ...

author keywords: Vascular Ehlers-Danlos syndrome; Cell derived matrix; Collagen III; Mechanotransduction; ECM mechanics; Viscoelasticity
TL;DR: This work generates fibrous, collagen-rich ECM from primary donor cells from patients with vascular Ehlers-Danlos syndrome, a disease caused by mutations in the gene that encodes collagen III, and observes that ECM grown from vEDS patients is characterized by unique mechanical signatures, including altered viscoelastic properties. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (OpenAlex)
Source: Web Of Science
Added: August 7, 2023

2023 journal article

Redox-active endosomes mediate α5β1 integrin signaling and promote chondrocyte matrix metalloproteinase production in osteoarthritis

SCIENCE SIGNALING, 16(809).

By: M. Miao *, Q. Su *, Y. Cui *, E. Bahnson *, G. Li *, M. Wang *, Y. Yang *, J. Collins * ...

TL;DR: Fragments of extracellular matrix proteins stimulate chondrocytes to produce proteases, thus perpetuating cartilage degradation, and this signaling mechanism not only amplifies the production of matrix-degrading proteases but also establishes a self-perpetuating cycle that contributes to the ongoing degradation of cartilage matrix in osteoarthritis. (via Semantic Scholar)
Source: Web Of Science
Added: March 25, 2024

2023 journal article

Yes-associated protein nuclear translocation promotes anabolic activity in human articular chondrocytes

OSTEOARTHRITIS AND CARTILAGE, 31(8), 1078–1090.

By: Y. Cui *, M. Miao *, M. Wang *, Q. Su *, K. Qiu*, L. Arbeeva*, S. Chubinskaya*, B. Diekman n, R. Loeser *

author keywords: Yes-associated protein; Nuclear translocation; Differential phosphorylation; Mechanotransduction; Chondrocytes
TL;DR: YAP chondrocyte nuclear translocation is regulated by differential phosphorylation in response to anabolic and catabolic stimuli and may contribute to reduced anabolic activity and promotion of further cartilage loss. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: August 28, 2023

2022 article

3D chromatin structure in chondrocytes identifies putative osteoarthritis risk genes

Thulson, E., Davis, E. S., D'Costa, S., Coryell, P. R., Kramer, N. E., Mohlke, K. L., … Phanstiel, D. H. (2022, September 13). GENETICS.

By: E. Thulson*, E. Davis *, S. D'Costa*, P. Coryell*, N. Kramer*, K. Mohlke *, R. Loeser *, B. Diekman n, D. Phanstiel *

author keywords: 3D chromatin structure; genome-wide association studies; osteoarthritis; genomics
MeSH headings : Humans; Chondrocytes; Fibronectins / genetics; Fibronectins / metabolism; Genome-Wide Association Study; Osteoarthritis / genetics; Osteoarthritis / metabolism; Chromatin / genetics; Chromatin / metabolism
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Source: Web Of Science
Added: December 5, 2022

2022 article

Comet assay for quantification of the increased DNA damage burden in primary human chondrocytes with aging and osteoarthritis

Copp, M. E., Chubinskaya, S., Bracey, D. N., Shine, J., Sessions, G., Loeser, R. F., & Diekman, B. O. (2022, August 22). AGING CELL.

By: M. Copp n, S. Chubinskaya *, D. Bracey *, J. Shine *, G. Sessions *, R. Loeser *, B. Diekman n

author keywords: arthritis; cartilage; single-cell gel electrophoresis
MeSH headings : Adult; Aged; Aging / genetics; Cadaver; Cartilage, Articular / metabolism; Cells, Cultured; Chondrocytes / metabolism; Comet Assay; DNA Damage / genetics; Humans; Middle Aged; Osteoarthritis / genetics; Osteoarthritis / metabolism
TL;DR: This study supports the investigation of mechanisms by which hypo‐replicative cell types accumulate high levels of damage in chondrocytes obtained from cadaveric donors of a wide age range and shows that most of the accumulated damage is in the form of strand breaks as opposed to alkali‐labile base damage. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: September 6, 2022

2022 journal article

Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus)

PLOS ONE, 17(11).

By: M. Williams n , R. Meyers n, L. Braxton n, B. Diekman n & B. Lascelles  n

Ed(s): A. Wijnen

MeSH headings : Rats; Animals; Rats, Sprague-Dawley; Lameness, Animal; Disease Models, Animal; Osteoarthritis / complications; Pain / complications; Models, Anatomic; Outcome Assessment, Health Care
TL;DR: The pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: November 22, 2022

2021 journal article

Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice

NATURE COMMUNICATIONS, 12(1).

By: E. Novais *, V. Tran *, S. Johnston *, K. Darris*, A. Roupas*, G. Sessions *, I. Shapiro *, B. Diekman*, M. Risbud *

MeSH headings : Aggrecans / metabolism; Aging / drug effects; Aging / metabolism; Animals; Annulus Fibrosus / drug effects; Annulus Fibrosus / metabolism; Annulus Fibrosus / pathology; Cell Survival / drug effects; Cellular Senescence / drug effects; Dasatinib / therapeutic use; Extracellular Matrix / drug effects; Extracellular Matrix / metabolism; Fibrosis; Inflammation; Intervertebral Disc Degeneration / drug therapy; Intervertebral Disc Degeneration / metabolism; Intervertebral Disc Degeneration / pathology; Mice; Mice, Inbred C57BL; Nucleus Pulposus / drug effects; Nucleus Pulposus / metabolism; Nucleus Pulposus / pathology; Phenotype; Quercetin / therapeutic use; Transcriptome / drug effects
TL;DR: Long term treatment with senolytic compounds Dasatinib and Quercetin reduces disc senescence burden and ameliorates age-dependent degeneration in mice, and suggests that senolytics may provide an attractive strategy to mitigating age- dependent disc degeneration. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Source: Web Of Science
Added: September 20, 2021

2021 journal article

Sirtuin 6 (SIRT6) regulates redox homeostasis and signaling events in human articular chondrocytes

FREE RADICAL BIOLOGY AND MEDICINE, 166, 90–103.

By: J. Collins *, M. Kapustina *, J. Bolduc*, J. Pike*, B. Diekman n, K. Mix*, S. Chubinskaya*, E. Eroglu * ...

author keywords: Sirtuin; Aging; Oxidative stress; Antioxidant; Redox signaling; Osteoarthritis
MeSH headings : Aged; Animals; Biological Phenomena; Cartilage, Articular / metabolism; Chondrocytes; Homeostasis; Humans; Hydrogen Peroxide / metabolism; Mice; Oxidation-Reduction; Oxidative Stress; Sirtuins / genetics; Sirtuins / metabolism
TL;DR: It is demonstrated that SIRT6 activity is altered with age and oxidative stress conditions associated with aging, and contributes to chondrocyte redox homeostasis by regulating specific members of the Prx catalytic cycle. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: April 12, 2021

2021 journal article

The combination of mitogenic stimulation and DNA damage induces chondrocyte senescence

OSTEOARTHRITIS AND CARTILAGE, 29(3), 402–412.

By: M. Copp n, M. Flanders  n, R. Gagliardi n, J. Gilbertie n, G. Sessions *, S. Chubinskaya*, R. Loeser *, L. Schnabel n, B. Diekman n

author keywords: SA-beta-gal; DNA damage; Osteoarthritis; Aging; TGF- beta 1; bFGF
MeSH headings : Animals; Ankle Joint; Cartilage, Articular / cytology; Cartilage, Articular / drug effects; Cartilage, Articular / metabolism; Cellular Senescence / drug effects; Cellular Senescence / genetics; Chemokine CCL2 / drug effects; Chemokine CCL2 / genetics; Chondrocytes / drug effects; Chondrocytes / metabolism; Cyclin-Dependent Kinase Inhibitor p16 / drug effects; Cyclin-Dependent Kinase Inhibitor p16 / metabolism; DNA Damage / genetics; Fibroblast Growth Factor 2 / pharmacology; Gene Expression / drug effects; Histones / drug effects; Histones / metabolism; Horses; Humans; In Vitro Techniques; Inflammation / genetics; Insulin-Like Growth Factor Binding Protein 3 / drug effects; Insulin-Like Growth Factor Binding Protein 3 / genetics; Interleukin-6 / genetics; Matrix Metalloproteinase 13 / drug effects; Matrix Metalloproteinase 13 / genetics; Mitogens / pharmacology; Stifle; Transforming Growth Factor beta1 / pharmacology; beta-Galactosidase / drug effects; beta-Galactosidase / metabolism
TL;DR: Treatment of cartilage explants with mitogenic stimuli in the context of cellular damage reliably induces high levels of SA-β-gal activity and other senescence markers, which provides a physiologically relevant model system to investigate the mechanisms of senescences induction. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: March 29, 2021

2020 journal article

Arp2/3 inactivation causes intervertebral disc and cartilage degeneration with dysregulated TonEBP-mediated osmoadaptation

JCI INSIGHT, 5(4).

By: S. Tessier *, A. Doolittle*, K. Sao *, J. Rotty *, J. Bear, V. Ulici*, R. Loeser *, I. Shapiro *, B. Diekman n, M. Risbud *

MeSH headings : Actin-Related Protein 2-3 Complex / antagonists & inhibitors; Actin-Related Protein 2-3 Complex / metabolism; Adaptation, Physiological; Animals; Cartilage, Articular / metabolism; Cartilage, Articular / pathology; Intervertebral Disc / metabolism; Intervertebral Disc / pathology; Mice; Mice, Mutant Strains; Osmoregulation; Transcription Factors / metabolism
TL;DR: Findings suggest that Arp2/3 plays a critical role in cartilaginous tissues through the regulation of cell-extracellular matrix interactions and modulation of TonEBP-mediated osmoadaptation. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: March 23, 2020

2020 journal article

Deletion ofJNKEnhances Senescence in Joint Tissues and Increases the Severity of Age-Related Osteoarthritis in Mice

ARTHRITIS & RHEUMATOLOGY, 72(10), 1679–1688.

By: R. Loeser *, K. Kelley*, A. Armstrong *, J. Collins *, B. Diekman n & C. Carlson *

MeSH headings : Aging / metabolism; Animals; Cartilage, Articular / metabolism; Cellular Senescence / genetics; Chondrocytes / metabolism; Disease Models, Animal; Knee Joint / metabolism; Matrix Metalloproteinase 13 / metabolism; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 8 / genetics; Mitogen-Activated Protein Kinase 8 / metabolism; Mitogen-Activated Protein Kinase 9 / genetics; Mitogen-Activated Protein Kinase 9 / metabolism; Osteoarthritis / diagnosis; Osteoarthritis / genetics; Osteoarthritis / metabolism; Severity of Illness Index
TL;DR: To determine the role of JNK signaling in the development of osteoarthritis (OA) induced by joint injury or aging in mice, a large number of mice were sacrificed and the JNK gene was switched off. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: September 14, 2020

2020 article

Dynamic interplay between connective tissues and the surrounding environment during aging

Diekman, B. O. C. (2020, January 2). CONNECTIVE TISSUE RESEARCH, Vol. 61, pp. 1–3.

By: B. Diekman*

MeSH headings : Aging / physiology; Connective Tissue / physiology; Humans
TL;DR: The theme of this special issue of Connective Tissue Research is the dynamic interplay between connective tissues and the surrounding environment during aging, and Zhu and colleagues provide a compelling manuscript that includes both conceptual frameworks derived from evolutionary biology and ecology and experimental data on redox regulation. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: December 16, 2019

2020 journal article

Engineered Cartilage from Human Chondrocytes with Homozygous Knockout of Cell Cycle Inhibitor p21

TISSUE ENGINEERING PART A, 26(7-8), 441–449.

By: S. D'Costa*, M. Rich  n & B. Diekman n

author keywords: genome editing; CRISPR; regeneration; tissue engineering
MeSH headings : Blotting, Western; Chondrocytes / cytology; Chondrocytes / metabolism; Clustered Regularly Interspaced Short Palindromic Repeats / genetics; Cyclin-Dependent Kinase Inhibitor p21 / genetics; Cyclin-Dependent Kinase Inhibitor p21 / metabolism; Gene Editing; Glycosaminoglycans / metabolism; Humans; Immunohistochemistry; Polymerase Chain Reaction; Tissue Engineering / methods
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: December 9, 2019

2020 journal article

Microfluidics for the study of mechanotransduction

JOURNAL OF PHYSICS D-APPLIED PHYSICS, 53(22).

By: C. Griffith  n, S. Huang n, C. Cho  n, T. Khare  n, M. Rich  n, G. Lee*, F. Ligler n, B. Diekman n, W. Polacheck n

author keywords: microfluidics; mechanotransduction; mechanobiology; microfabrication; cell adhesion; biofluids; microdevices
TL;DR: An overview of the main mechanotransduction pathways that function at sites of cell adhesion are given, and examples of how microfluidics can be used to apply both solid forces and fluid forces to cells are presented. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: April 20, 2020

2020 personal communication

Reply

Loeser, R. F., Collins, J. A., Diekman, B. O., & Carlson, C. S. (2020, December).

By: R. Loeser *, J. Collins *, B. Diekman n & C. Carlson *

MeSH headings : Animals; Mice; Osteoarthritis
TL;DR: Results indicated that knockout of JNK signaling is able to promote senescence in joint tissues and up-regulate the severity of age-related OA, which shows the potential of targeting J NK signaling to treat OA. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: October 19, 2020

2019 journal article

Cells exhibiting strong p16(INK4a) promoter activation in vivo display features of senescence

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116(7), 2603–2611.

By: J. Liu *, G. Souroullas *, B. Diekman n, J. Krishnamurthy*, B. Hall *, J. Sorrentino *, J. Parker *, G. Sessions *, A. Gudkov *, N. Sharpless *

author keywords: senescence; cdkn2a; aging
MeSH headings : Animals; Cell Proliferation; Cellular Senescence / genetics; Cyclin-Dependent Kinase Inhibitor p16 / genetics; Enzyme Activation; Fibroblasts / metabolism; Half-Life; Humans; Mice; Phenotype; Promoter Regions, Genetic; RNA, Messenger / genetics; beta-Galactosidase / metabolism
TL;DR: A reporter allele is described, p16tdTom, enabling the in vivo identification and isolation of cells featuring high-level activation of the p16INK4a promoter, displaying characteristics of senescence. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: February 25, 2019

2019 journal article

p16(Ink4a) deletion in cells of the intervertebral disc affects their matrix homeostasis and senescence associated secretory phenotype without altering onset of senescence

MATRIX BIOLOGY, 82, 54–70.

By: E. Novais *, B. Diekman n, I. Shapiro * & M. Risbud *

author keywords: p16; p19; Ink4a; Senescence; Mouse models; Intervertebral disc degeneration; Aggrecan; Extracellular matrix; Nucleus pulposus; Aging; SASP
MeSH headings : Aggrecans / metabolism; Aging / genetics; Aging / metabolism; Animals; Cellular Senescence; Collagen / metabolism; Cyclin-Dependent Kinase Inhibitor p16 / genetics; Cyclin-Dependent Kinase Inhibitor p16 / metabolism; Disease Models, Animal; Extracellular Matrix / metabolism; Gene Deletion; Homeostasis; Humans; Intervertebral Disc Degeneration / genetics; Intervertebral Disc Degeneration / metabolism; Mice; Phenotype
TL;DR: Conditional loss of p16Ink4a reduces apoptosis, limits the SASP phenotype and alters matrix homeostasis of disc cells, and these results show that while, p 16Ink 4a is dispensable for induction and maintenance of senescence, conditional loss of cKO discs showed lower levels of SASP markers,IL-1β, IL-6, MCP1 and TGF-β1. (via Semantic Scholar)
UN Sustainable Development Goal Categories
15. Life on Land (OpenAlex)
Source: Web Of Science
Added: September 23, 2019

2018 review

Targeting aging for disease modification in osteoarthritis

[Review of ]. CURRENT OPINION IN RHEUMATOLOGY, 30(1), 101–107.

By: J. Colins, B. Diekman n & R. Loeser *

author keywords: aging; cell senescence; cell signaling; mitochondria; reactive oxygen species
MeSH headings : Aging / metabolism; Animals; Antioxidants / metabolism; Cellular Senescence; Gene Expression Regulation; Humans; Mitochondria / metabolism; NF-E2-Related Factor 2 / metabolism; Osteoarthritis / drug therapy; Osteoarthritis / metabolism; Oxidative Stress; Reactive Oxygen Species / metabolism; Signal Transduction
TL;DR: Preclinical studies suggest that targeting cellular senescence and/or mitochondrial dysfunction and the effects of excessive ROS may lead to novel interventions that could slow the progression of osteoarthritis. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: Web Of Science
Added: August 6, 2018

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