Inhibition of GDF8 (Myostatin) accelerates bone regeneration in diabetes mellitus type 2

Wallner, Christoph; Jaurich, Henriette; Wagner, Johannes Maximilian; Becerikli, Mustafa; Harati, Kamran; Dadras, Mehran; Lehnhardt, Marcus

doi:10.1038/s41598-017-10404-z

Cited by 42 publications

(32 citation statements)

References 47 publications

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“…For example, mice grown with FST overexpression via global knock-in exhibited an impaired bone structure (43). However, in adult diabetic mice, FST was shown to accelerate bone regeneration by inhibiting myostatin-induced osteoclastogenesis (44,45). Furthermore, it has been reported that FST down-regulates BMP2-driven osteoclast activation (46).…”

Section: Discussionmentioning

confidence: 99%

Gene Therapy for Follistatin Mitigates Systemic Metabolic Inflammation and Post-Traumatic Osteoarthritis in High-Fat Diet-Induced Obese Mice

Tang

Harasymowicz

et al. 2019

Preprint

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Obesity-associated inflammation and loss of muscle function play critical roles in the development of osteoarthritis (OA); thus, therapies that target muscle tissue may provide novel approaches to restoring metabolic and biomechanical dysfunction associated with obesity. Recent studies indicate that follistatin (FST), a protein which binds myostatin and activin, may have the potential to enhance muscle formation while neutralizing inflammation induced by these proteins. Here, we hypothesized that adeno-associated virus (AAV9) delivery of FST will enhance muscle formation and mitigate metabolic inflammation and knee OA caused by a high fat diet in mice. Obese mice receiving AAV-mediated FST delivery exhibited decreased inflammatory adipokines and cytokines systemically in the serum as well as locally in the joint synovial fluid. Regardless of diet, mice receiving FST gene therapy were protected from post-traumatic OA and bone remodeling induced by joint injury. While obesity disrupted the mitochondrial oxidative phosphorylation (OXPHOS) system in adipocytes, gene therapy for FST restored the key proteins involved in mitochondrial biogenesis, such as PPARγ coactivator 1α and AKT protein kinase 1, leading to the browning of white adipose tissue. Taken together, these findings suggest that FST gene therapy may provide a multifactorial therapeutic approach for injury-induced OA and metabolic inflammation in obesity.

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Section: Discussionmentioning

confidence: 99%

Gene Therapy for Follistatin Mitigates Systemic Metabolic Inflammation and Post-Traumatic Osteoarthritis in High-Fat Diet-Induced Obese Mice

Tang

Harasymowicz

et al. 2019

Preprint

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“…Recently, the importance of myostatin for bone regeneration has been considered [ 106 ]. Myostatin inhibition restored bone healing in diabetic animals [ 107 ]. Current resear proved that inflammation is a trigger for the interaction of myostatin in musculoskeletal injury.…”

Section: Commonalities and Differences In Healing Cascades Of Diffmentioning

confidence: 99%

Immunology Guides Skeletal Muscle Regeneration

Sass

Fuchs

Pumberger

et al. 2018

IJMS

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Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

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“…Myostatin ist ein von Myozyten sekretiertes Molekül der TGF-β-Proteinfamilie und wirkt hauptsächlich als autokriner Inhibitor der Myogenese und Osteogenese [6,7]. Eine Knockout-Mutation dieses Gens zeigt eine deutliche Muskelmassezunahme sowohl im Tier als auch im Menschen [8,9].…”

Section: Elevation Of Myostatin As a Potential Marker For Compartmentunclassified

Myostatin als potenzieller Marker für das Kompartmentsyndrom bei elektrischen Verletzungen

et al. 2019

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Zusammenfassung Einleitung Elektrische Unfälle und insbesondere daraus resultierende Kompartmentsyndrome sind herausfordernde Verletzungen in der klinischen Behandlung. Kreatinkinase (CK) und Myoglobin sind bekannte Laborparameter zur Bestimmung eines Kompartmentsyndroms. Methoden Wir haben Patienten mit elektrischen Verletzungen zwischen 2006 und 2016 in unserer Verbrennungsklinik untersucht. Wir wollten die Rolle von Myostatin als Marker für das Kompartmentsyndrom durch Serummessungen innerhalb von 24 h nach der Verletzung analysieren. Ergebnisse Wir haben Daten von 24 Patienten erhoben, die mit einer elektrischen Hochspannungsverletzung stationär behandelt wurden. Von diesen 24 Patienten konnten wir bei 14 Patienten Myostatinkonzentrationen messen. Während CK-MB (Kreatinkinase Typ Muscle-Brain [MB]) keine signifikante Korrelation mit einem Kompartmentsyndrom zeigte, zeigten CK und Myostatin einen stark signifikanten Anstieg. Interessanterweise war Myostatin bei elektrischen Verletzungen signifikant erhöht, jedoch nicht bei Verbrennungen, während CK keinen signifikanten Unterschied zeigte. Schlussfolgerung Neben CK kann Myostatin somit als zuverlässiger Frühmarker für das Kompartmentsyndrom bei elektrischen Verletzungen dienen.

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Inhibition of GDF8 (Myostatin) accelerates bone regeneration in diabetes mellitus type 2

Cited by 42 publications

References 47 publications

Gene Therapy for Follistatin Mitigates Systemic Metabolic Inflammation and Post-Traumatic Osteoarthritis in High-Fat Diet-Induced Obese Mice

Gene Therapy for Follistatin Mitigates Systemic Metabolic Inflammation and Post-Traumatic Osteoarthritis in High-Fat Diet-Induced Obese Mice

Immunology Guides Skeletal Muscle Regeneration

Myostatin als potenzieller Marker für das Kompartmentsyndrom bei elektrischen Verletzungen

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