Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CSF1-R inhibition attenuates posttraumatic osteoarthritis and quadriceps atrophy following ligament injury II

ABSTRACT: Knee osteoarthritis contributes substantially to worldwide disability. Post-traumatic osteoarthritis (PTOA) develops secondary to a joint injury, such as ligament rupture, and there is increasing evidence suggesting a key role for inflammation in the etiology of PTOA and associated functional deficits. Colony stimulating factor 1 receptor (CSF1-R) has been implicated in the pathogenesis of musculoskeletal degeneration following anterior cruciate ligament (ACL) injury. We sought to assess the efficacy CSF1-R inhibition to mitigate muscle and joint pathology in a mouse model of PTOA. Four-month-old mice were randomized to receive a CSF1-R inhibitor and studied for 7 or 28 days after joint injury. Additionally, we profiled synovial fluid samples for CSF1-R from patients with injury to their ACL. Transcriptomic analysis of quadriceps muscle and articular cartilage in CSF1-R inhibitor-treated animals at 7 days after injury revealed elevated chondrocyte differentiation within articular cartilage and enhanced metabolic and contractile gene expression within skeletal muscle. At 28 days post-injury, CSF1-R inhibition attenuated PTOA severity and mitigated skeletal muscle atrophy. Patient synovial fluid CSF1-R levels correlated with matrix metalloproteinase 13, a prognostic marker and molecular effector of PTOA. Our findings support an opportunity for CSF1-R targeting to mitigate the severity of PTOA and muscle atrophy after joint injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE275958 | GEO | 2025/06/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CSF1-R inhibition attenuates posttraumatic osteoarthritis and quadriceps atrophy following ligament injury I

Project description:Knee osteoarthritis contributes substantially to worldwide disability. Post-traumatic osteoarthritis (PTOA) develops secondary to a joint injury, such as ligament rupture, and there is increasing evidence suggesting a key role for inflammation in the etiology of PTOA and associated functional deficits. Colony stimulating factor 1 receptor (CSF1-R) has been implicated in the pathogenesis of musculoskeletal degeneration following anterior cruciate ligament (ACL) injury. We sought to assess the efficacy CSF1-R inhibition to mitigate muscle and joint pathology in a mouse model of PTOA. Four-month-old mice were randomized to receive a CSF1-R inhibitor and studied for 7 or 28 days after joint injury. Additionally, we profiled synovial fluid samples for CSF1-R from patients with injury to their ACL. Transcriptomic analysis of quadriceps muscle and articular cartilage in CSF1-R inhibitor-treated animals at 7 days after injury revealed elevated chondrocyte differentiation within articular cartilage and enhanced metabolic and contractile gene expression within skeletal muscle. At 28 days post-injury, CSF1-R inhibition attenuated PTOA severity and mitigated skeletal muscle atrophy. Patient synovial fluid CSF1-R levels correlated with matrix metalloproteinase 13, a prognostic marker and molecular effector of PTOA. Our findings support an opportunity for CSF1-R targeting to mitigate the severity of PTOA and muscle atrophy after joint injury.

2025-06-25 | GSE275957 | GEO

Single cell level characterization of injury-induced immune changes in 10-week-old and 95-week-old C57BL/6 knee joints

Project description:Post-traumatic Osteoarthritis (PTOA) occurs in about half of individuals who sustained articular injuries including tibial plateau fracture, meniscus tear, or an anterior cruciate ligament (ACL) rupture. Damage-associated molecular pattern (DAMP) proteins are typically secreted from injured or dying cells of the synovial joint into the surrounding environment immediately following injury which in turn recruit leukocytes to mediate debris clean-up and repair. Prior bulk RNA-seq experiments exploring organismal age-related differences following ACL rupture found an increased expression of inflammatory-response related genes in 95-week-old mice relative to 10-week-old mice. Using single-cell RNA sequencing technology we temporally explored differences in immune cell infiltration in the synovial joint in 10-week-old and 95-week-old C57BL/6 mice.

2025-07-05 | GSE236843 | GEO

Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis

Project description:Osteoarthritis (OA) is the most common joint disease, affecting over 300 million people world-wide. Accumulating evidence attests to the important roles of immune system in OA pathogenesis. Understanding the role of various immune cells in joint degeneration or joint repair after injury is helpful for improving therapeutic strategies for treating OA. Post-traumatic osteoarthritis (PTOA) develops in ~50% of individuals who have experienced an articular trauma like an anterior cruciate ligament (ACL) rupture. Here, using highly sensitive single-cell RNA sequencing technology, we delineated the temporal dynamics of immune cell accumulation in the mouse knee joint after ACL rupture.

2022-07-18 | GSE200843 | GEO

Comparative Transcriptomics of STR/ort, C57BL/6 and MRL/MpJ Knee Joints

Project description:Injuries to the anterior cruciate ligament (ACL) often result in post-traumatic osteoarthritis (PTOA). PTOA accounts for ~12% of all osteoarthritis (OA) cases, yet the mechanisms contributing to OA after joint injury are not well understood. To better understand the molecular mechanisms behind PTOA development following ACL injury, we profiled ACL injury-induced gene expression changes in knee joints of three mouse strains with varying susceptibility to PTOA: STR/ort (highly susceptible), C57BL/6 (moderately susceptible) and super-healer MRL/MpJ (not susceptible) and identified genes differentially expressed between these strains at 0-day [before injury], 1-day, 1-week, and 2-weeks post-injury. This study highlights many new potential therapeutic targets and OA biomarkers.

2018-11-28 | GSE112641 | GEO

Single cell level characterization of immune cells in 10-week-old C57BL/6 knee joints and femur bone marrow

Project description:Post-traumatic Osteoarthritis (PTOA) occurs in about half of individuals who sustained articular injuries including tibial plateau fracture, meniscus tear, or an anterior cruciate ligament (ACL) rupture. We utilize a noninvasive tibial compression injury (TCI) model that can closely replicate the anterior cruciate ligament rupture in patients, which reliably initiates PTOA development. In other studies we utilize single-cell RNA sequencing to temporally explore differences in immune cell infiltration following injury. Although extreme care is taken during immune cell isolation to prevent contamination from bone marrow, we also wanted to rule out the possibility of contamination from bone marrow immune cells in our knee joint samples. Therefore, we proceeded to compare the neutrophil populations from uninjured joint (joint) to bone marrow (marrow) to identify the similarities and differences between these populations.

2025-07-05 | GSE236844 | GEO

Single-cell sequencing of murine articular cartilage

Project description:Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage loss, bone remodeling, synovial inflammation, and significant joint pain, often resulting in disability. Injury to the synovial joint such as the anterior cruciate ligament (ACL) tear is the major cause of OA in young adults. Currently, there are no approved therapies available to prevent joint degeneration or rebuild articular cartilage destroyed by OA, primarily because our understanding of the cellular and molecular changes that contribute to joint damage is very limited. The synovial joint is a complex structure composed of several tissues including articular cartilage, subchondral bone, synovium, synovial fluid, and tensile tissues including tendons and ligaments. In the present study, using single-cell RNA sequencing (scRNA-seq), we examined the cellular heterogeneity in articular cartilage from mouse knee joints and determined the knee joint injury-induced early molecular changes in the chondrocytes that could contribute to OA.

2021-06-19 | GSE172500 | GEO

Single cell level characterization of injury-induced immune changes in MRL/MpJ knee joints

Project description:Post traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and connective tissues. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus or by intra-articular fractures. In humans, ~50% of joint injuries progress to chronic PTOA, while the rest spontaneously resolve. To understand molecular programs contributing to PTOA development, we examined injury-induced fluctuations in immune cell populations and transcriptional shifts by single-cell sequencing of synovial joints in PTOA -susceptible C57BL6/J (B6) and -resistant MRL/MpJ (MRL) mice. A potent myeloid driven anti-inflammatory response was discovered in MRL injured joints that significantly contrasted the pro-inflammatory signaling seen in B6 joints. We found Trem2+ macrophages classically described as M2 (CD206+Trem2+) to be enriched in the uninjured joints of MRL mice, and these populations were consistently elevated in this strain, post injury. To evaluate whether Trem2 is essential to macrophage-mediated homeostasis in the joint, we examined Trem2 deficient mice and determined that these mice develop spontaneous OA. Overall, these data suggest that the PTOA resistant MRL mouse strain displays enhanced capacity of clearing debris and apoptotic cells induced by inflammation after injury due to an increase in activated macrophages within the synovial tissue and joint space. Furthermore, we showed that Trem2 is essential for preserving cartilage homeostasis in B6, and we postulate that the elevated levels of Trem2+ joint-resident macrophages in MRL are in part responsible for the PTOA-resistant phenotype in this strain.

2024-12-31 | GSE220167 | GEO

Genetic and monoclonal antibody blockade of GDF8 enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following ligament injury [cartilage]

Project description:Background: Musculoskeletal disorders contribute to a substantial proportion of disability among people worldwide. Anterior cruciate ligament (ACL) tears are among the most frequent knee injuries, and a majority of patients will go on to develop knee osteoarthritis within 10 years. Traditional rehabilitation following injury has limited success restoring muscle strength and mitigating the onset of posttraumatic knee osteoarthritis. Growth differentiation factor 8 (GDF8), or myostatin, is a myokine that has been implicated in the pathogenesis of musculoskeletal degeneration following ACL injury. This study investigated GDF8 levels in injured human skeletal muscle and serum and compared the efficacy of a humanized monoclonal GDF8 antibody against a placebo in a mouse model of injury-induced osteoarthritis (surgically induced ACL tear). Muscle GDF8 peaks rapidly following ACL injury, and early induction of GDF8 in skeletal muscle was predictive of atrophy, weakness and periarticular bone loss in patients six months following surgical ACL reconstruction. GDF8 antibody administration at the time of injury substantially reduced muscle atrophy, weakness and fibrosis in the mouse ACL injury model. GDF8 antibody treatment rescued the skeletal muscle and articular cartilage transcriptomic response to ACL injury and attenuated the severity of injury-induced knee osteoarthritis. Subcutaneous treatment with GDF8 antibody also diminished loss of periarticular bone microarchitecture. Genetic deletion of GDF8 neutralized musculoskeletal deficits in response to ACL injury. Our findings support an opportunity for rapid targeting of GDF8 to enhance functional musculoskeletal injury recovery and mitigate the development posttraumatic knee osteoarthritis, which could substantially reduce the disability burden associated with this injury.

2023-12-06 | GSE230736 | GEO

Genetic and monoclonal antibody blockade of GDF8 enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following ligament injury [quadricep]

2023-12-06 | GSE230708 | GEO

Synovial fluid proteomics from serial aspiration of ACL injured knees identifies candidate biomarkers for osteoarthritis

Project description:Patients with anterior cruciate ligament (ACL) tears have a significantly increased risk for developing knee osteoarthritis. These injuries often result in a knee effusion in response to the injury. Early changes in these effusions could be informative regarding initial steps in the development of post traumatic osteoarthritis. The purpose of this study was to test the hypothesis that the proteomics of knee synovial fluid changes over time following ACL injury.

2022-06-23 | MSV000089716 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data