Muscle cell secretom and bone cells interplay in osteosarcopenia (MiKOSA)

Osteosarcopenia (OSA) affects 5-37% of community-dwelling older people (≥65 years) and is diagnosed at even higher rates in people with low-energy trauma (osteoporotic) bone fractures (7.1–96.3%). There are no diagnostic biochemical markers available and no approved pharmacological agents for treatment of sarcopenia so far. With the present project, we aim to evaluate the effects of muscle derived factors on osteoporotic bone cells in order to find the crucial molecules and signalling pathways in bone as potential therapeutic or diagnostic targets in OSA. To achieve the aim, we will recruit older women with an osteoporotic bone fracture with (n=50) and without sarcopenia (n=50) who will undergo hip replacement surgery. This will allow us to collect bone, muscle and blood samples from the same patients. Muscle-bone interplay will be studied at three different levels, from patient data, through ex vivo tissue analysis and in vitro isolated cell analysis. The project is divided into four parts. The work package 1 (WP1) addresses patient and data recruitment, in vivo bone and muscle evaluation (e.g. DXA, grip strength, ...), tissue sample collection (bone, muscle, blood), which will result in a well characterised patient tissue bank. In WP2, the preparation and analyses (histology, gene expression, microCT) of the collected tissue are planned in order to assess the presence of OSA at tissue level. WP3 will focus on comparative transcriptome analyses of secretome-treated and untreated isolated bone cells (MSC and OB). The most significant genes (hits) obtained by these comparative transcriptome analyses will be functionally evaluated for their role in osteoporosis/sarcopenia in order to confirm the relevance of potential new therapeutic or diagnostic targets of OSA. WP4 is aimed to coordinate activities between six research groups at four partner institutions and take care of results dissemination and project reports. Our innovative approach to treat the bone cells with the muscle secretome was not employed or described up to now, but represents an appropriate model for studying the communication between muscle and bone cells in OSA.