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Significance MSTN, a member of the TGF-β family, has been widely shown to suppress muscle growth, leading to an intense effort being directed at targeting MSTN to treat patients with muscle loss. GDF11 is another TGF-β family member closely related to MSTN, but its postnatal function is less clear. Using conditional knockout techniques, we show that GDF11 enhances bone mass in contrast to MSTN, emphasizing that MSTN/GDF11 inhibitors, such as FST, can induce adverse effects on bone through GDF11 inhibition. Because most MSTN inhibitors also inhibit GDF11 due to the high sequence similarity between MSTN and GDF11, our findings suggest that their opposing roles must be carefully considered when developing MSTN inhibitors for clinical applications.

GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone