Synovial fluid proteomics from serial aspiration of ACL injured knees identifies candidate biomarkers for osteoarthritis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive Plus
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Muhammad Farooq Rai
PROVIDER: MSV000089716 | MassIVE | Thu Jun 23 13:44:00 BST 2022
SECONDARY ACCESSION(S): PXD034860
REPOSITORIES: MassIVE
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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
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 | GSE230708 | GEO
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.
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Project description:The anterior cruciate ligament (ACL) is an essential stabilizer of the tibiofemoral articulation. ACL tears often lead to functional instability and are associated with an increased risk for osteoarthritis. The healing potential of the injured ACL is poorly understood and is considered to be limited. Transcriptome-wide expression profiles of 24 human ACL remnants recovered at the time of surgical reconstruction were analyzed utilizing the Agilent human 8x60K microarray platform. Gene ontology was performed on differentially expressed transcripts based on time-from-injury (acute, <3 months; intermediate, 3-12 months; chronic, >12 months). A subset of transcripts was validated via microfluidic digital polymerase-chain-reaction. Expression of periostin, a highly differentially expressed transcript, was tested by immunohistochemistry. Numerous transcripts covering important functional classifications were differentially expressed by time-from-injury. In acute tears, processes representing angiogenesis were repressed while those representing stem-cell differentiation were elevated. In intermediate tears, processes representing stem-cell proliferation concomitant with cellular component organization/cellular localization were elevated. In chronic tears, processes denoting myosin filament organization were elevated while those representing cellular component organization/cell localization and extracellular matrix organization were repressed. Expression levels of periostin were down-regulated in chronic tears compared to acute (42-fold) and intermediate (29-fold) tears. Immunohistochemistry confirmed a decline in periostin expression in tissues from chronic tears. These findings suggest an initial attempt of the injured ACL to repair, which declines with time-from-injury. These findings have implications for efforts to repair the ACL and may be relevant for reconstruction of the ACL. The functional role of periostin in ACL injuries, and the potential implication for surgical treatment, warrants further investigation. Total RNA obtained frominjured anterior cruciate ligament (ACL) tissues from pateints undergoing ACL surgery.
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2014-01-22 | E-MTAB-1323 | biostudies-arrayexpress
Project description:Despite ample evidence demonstrating that anterior cruciate ligament (ACL) and meniscus tears are associated with the development of knee osteoarthritis (OA), the contributing factors remain unknown. Synovial inflammation has recently been recognized as a pivotal factor in the pathogenesis of OA. However, there is a lack of data on synovial profiles after ACL or meniscus injuries, which may contribute to posttraumatic OA (PTOA). We performed RNA-seq of 3 inflamed synovial biopsy samples vs 3 normal synovial biopsy samples following ACL and/or meniscus injuries. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein–protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences between the inflamed and normal groups.Next, competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and quantitative real-time polymerase chain reaction (RT–PCR) results. The association of the identified DEGs with the levels of infiltrating immune cells was explored using Pearson correlation analysis in R software. We aimed to provide greater insights into molecular mechanisms and biologic pathways in synovitis that could regulate post-trauma osteoarthritis progression.
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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
Project description:Small RNA isolated from synovial fluid of the metacarpophalangeal joints of horses. Horses either had minimal signs of osteoarthritis based on macroscopic and microscopic joint scoring or early (mild) osteoarthritis. Differential expression of small non-coding RNAs was undertaken.
2020-06-30 | E-MTAB-8409 | biostudies-arrayexpress
Project description:Injury to anterior cruciate ligament (ACL) is common in young individuals and a frequent cause of functional instability and early onset of osteoarthritis. The healing potential of an injured ACL is known to decay over time. The molecular origin of this healing deficiency largely remains elusive but plausibly involves gene transcripts associated with tissue healing. To explore this possibility, we set out to identify transcript expression differences in injured ACL remnants recovered at the time of surgical reconstruction, via microarray (n=24) and RNA-seq (n=8) technologies in transcriptome profiling. We found that time-from-injury was an important determinant of changes in gene expression signatures predominately resulting in repression of several biological processes as identified by gene ontology. The most interesting observation was a time-dependent decline in the gene transcripts as well as the biological processes common to both microarray and RNA-seq analyses. Compared to acute tears, in chronic several important biological processes were namely extracellular matrix organization, angiogenesis, cell adhesion, wound healing, mesenchyme transition, and response to hypoxia. Furthermore, the cross-platform concordance in terms of differentially expressed transcripts or enriched pathways was linearly correlated (r=0.64). Microfluidic digital PCR confirmed the expression of selected differentially expressed transcripts. These intriguing findings suggest an initial attempt of the injured ACL to repair, which drops with time. These findings have implications for efforts to repair the ACL and may be relevant for its reconstruction. These findings also emphasize the utility of differentially expressed transcripts as prognostic biomarkers in patients with ACL injury. Examination of transcript expression differences by time-from-injury in anterior cruciate ligament
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Project description:Comparison of differential expression of small-noncoding RNAs between healthy and osteoarthritis diseased anterior cruciate ligament
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