GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation

Abstract

Osteoporosis is an age-related disease that affects millions of people. Growth differentiation factor 11 (GDF11) is a secreted member of the transforming growth factor beta (TGF-β) superfamily. Deletion of Gdf11 has been shown to result in a skeletal anterior–posterior patterning disorder. Here we show a role for GDF11 in bone remodelling. GDF11 treatment leads to bone loss in both young and aged mice. GDF11 inhibits osteoblast differentiation and also stimulates RANKL-induced osteoclastogenesis through Smad2/3 and c-Fos-dependent induction of Nfatc1. Injection of GDF11 impairs bone regeneration in mice and blocking GDF11 function prevents oestrogen-deficiency-induced bone loss and ameliorates age-related osteoporosis. Our data demonstrate that GDF11 is a previously unrecognized regulator of bone remodelling and suggest that GDF11 is a potential target for treatment of osteoporosis.

Ubiquitin‐specific protease USP 34 controls osteogenic differentiation and bone formation by regulating BMP 2 signaling

“…At 10 and 21 days post‐fracture, samples were collected for radiography, microCT scanning, and histology analysis. For femoral cortical bone defect, a 1.0 mm hole was generated using a round bur (Komet ® , Germany) operating at 10,000 rpm under saline irrigation (Liu et al , ,c). Samples were harvested 2 weeks after the surgery.…”

Growth differentiation factor 11 worsens hepatocellular injury and liver regeneration after liver ischemia reperfusion injury

“…Recently, the rejuvenating effect of GDF11 was called into question by Egerman et al (5), who demonstrated that GDF11 increased with age and inhibited muscle regeneration. Correspondingly, recent studies demonstrated that GDF11 had no rejuvenating effect on aged skeletal muscle satellite cells (18) or on aging-related pathologic hypertrophy (19), but induced bone loss (20), striated muscle atrophy (21), and cardiac and skeletal muscle dysfunction and wasting (22). Furthermore, elevated GDF11 is a risk factor for age-related frailty and disease in humans (23).…”

INO80 is Required for Osteogenic Differentiation of Human Mesenchymal Stem Cells

“…The cells were then stained with 1% Alizarin red S (pH 4.2, Sigma-Aldrich) for up to 5 minutes at room temperature15. Images of MSC stained with ARS were captured and stored digitally.…”