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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

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

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

2025-06-25 | GSE275958 | 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

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

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

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

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

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