In addition, IGF-1 is able to counteract the effects of myostatin

In addition, IGF-1 is able to counteract the effects of myostatin, a member of the TGFβ family

involved in muscle atrophy [23]. The hypothesis that Akt is implicated also in OP-related muscle atrophy is supported by our Western blot analysis, showing a significant reduction of Akt levels in OP atrophic muscles, compared to OA muscles. In fact, similarly to other metabolic myopathies, the decline of specific 3-Methyladenine in vitro hormones, including IGF-1, occurring in OP might downregulate IGF-1/PI3K/Akt activity, leading to muscle atrophy. Moreover, since IGF-1/PI3K/Akt controls glucose uptake in skeletal muscle [10], its downregulation could affect mainly glycolytic fibers (type II), whereas oxidative fibers (type I) tend to be more resistant to atrophy, because of their capacity of utilizing

other substrates than glucose to produce energy. Downstream mediators of Akt, such as mTOR, p70S6K, FoxO1, GSK3b, are to be studied to better clarify the IGF-1/PI3K/Akt role in OP-related muscle atrophy. An involvement of IGF-1/PI3K/Akt in OP, rather than in OA patients, could explain the muscle morphological differences found in those diseases. In fact, in OP patients, type II fiber atrophy is more prominent and selective as compared to OA and is related to severity of bone mass reduction. All patients in the OP group were examined for the first time on admission because of the hip fracture and did not refer any important

limitation in their physical daily activity. This leads to the hypothesis that OP muscle atrophy is independent from muscle disuse. The reduced bone density occurring in OP patients is due mainly to a decrease click here of circulating hormones, and according to the reduced Akt levels found in OP, we believe that OP muscle atrophy has the same pathogenesis. Conversely, our OA patients complained of a decline in their physical activity due to pain and functional impairment in the affected joint for some time before surgery, suggesting that their muscle atrophy could be mainly due to disuse. In confirmation of that, OA-related muscle atrophy was of lower extent, more homogeneous among fiber types (even if type II fibers are more liable to size variations), and correlated to the HHS and disease duration. Whether other factors, such as myostatin, systemic or local inflammatory mediators, cytokines, or inflammatory transcription factors, can contribute to the muscle atrophy present in OP and OA should be matter for further investigation. Our morphological study on vastus lateralis muscles failed to show, in both groups of patients, denervation features such as type grouping or angulated fibers, reported to be present in distal senescent muscle [24] but not in proximal muscle [25].

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