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

ABSTRACT: Genetic and monoclonal antibody blockade of GDF8 enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following ligament injury

PROVIDER: PRJNA962486 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24319200_1.fastq.gz	Fastqsanger.gz
	SRR24319200_2.fastq.gz	Fastqsanger.gz
	SRR24322700_1.fastq.gz	Fastqsanger.gz
	SRR24322700_2.fastq.gz	Fastqsanger.gz
	SRR24319201_1.fastq.gz	Fastqsanger.gz

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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

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

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

| PRJNA962183 | ENA

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

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

| PRJNA962492 | ENA

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-06 | GSE230737 | GEO

Gene expression profiling of human musculoskeletal tissue samples

Project description:We profiled gene expression of purified cell types isolated from 5 musculoskeletal tissues: tendon, bone, muscle, cartilage and ligament. We then performed WGCNA to identify tissue-specific transcription factors, signaling pathways and cell surface receptors. The sequencing data for muscle cells is made available here.

2018-03-29 | GSE106292 | GEO

Comprehensive proteomic comparison between native tendon and ligament and 3D tissue engineered tendon and ligament constructs

Project description:Tendons and ligaments are important biological structures in both humans and animals. They are part of dense connective tissue and are crucial to the functioning of the musculoskeletal system. However, they are commonly damaged due to age-related wear and tear, trauma or sports related incidents, which can lead to severe immobility for the individual and can lead to injury of other tissues and development of degenerative joint disease such as osteoarthritis. Tissue engineering can offer great potential in the treatment of tendon and ligament injury by seeking a biological replacement with fully regenerated autologenous tissue. This approach commonly involves an artificial ECM (scaffold) on which cell can proliferate and differentiate with subsequent new tissue generation. Fibrin is a natural scaffold with no expected toxic degradation or inflammatory reaction and can be used as an autologous scaffold for fibroblast from connective tissue to create a three dimensional structure. The purpose of this study was to compare the proteomic differences between native tendon, ligament and 3D tissue engineered tendon and ligament fibrin constructs.

2016-06-27 | PXD003094 | Pride

New protein from an unexpected ligament

Project description:This study describes the discovery of the gene responsible for differentiation of stem cells into ligament tissue. This important finding may lead to the development of treatments for gonarthrosis, rupture of the cruciate ligament and periodontal ligament, and ossification of the posterior longitudinal ligament. This study describes the discovery of the gene (A) responsible for differentiation of stem cells into ligament tissue. The transfection of this gene into mouse mesenchymal stem cells resulted in the formation of ligament-like connective tissue composed of parallel fibres. We performed microarray analysis of four samples: stem cells (sample1), ligament-like tissue from stem cells transfected with A (sample 4), ligament tissue from A-transgenic mice (sample 2) , and ligament tissue from wild type mice (sample 3).

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New protein from an unexpected ligament

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Expression data from human periodontal ligament

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