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.
Highlights
Osteoporosis is an age-related disease that affects millions of people
Growth differentiation factor 11 (GDF11) treatment leads to bone loss in young adult mice
We first examined the role of GDF11 in bone remodelling by administering young adult mice (9 week old) with daily intraperitoneal injections of recombinant GDF11 (rGDF11) (0.1 or 0.3 mg kg À 1 body weight; #120-11, PeproTech, Rocky Hill, NJ) or vehicle for 6 weeks
Summary
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-b) superfamily. Injection of GDF11 impairs bone regeneration in mice and blocking GDF11 function prevents oestrogen-deficiency-induced bone loss and ameliorates age-related osteoporosis. Systemic administration of rGDF11 in mice inhibits skeletal muscle regeneration[27] and fails to rescue age-related pathological cardiac hypertrophy[29]. These conflicting results led us to study whether GDF11 is associated with age-related bone loss. We show that injection of rGDF11 results in bone loss, as well as inhibition of bone regeneration in both young and aged mice. The delivery of a GDF11 blocking antibody prevents oestrogendeficiency-induced bone loss and ameliorates age-related osteoporosis, implying that GDF11 inhibition might be a potential therapeutic approach to prevent osteoporotic bone loss
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