Experimental models of musculoskeletal trauma demonstrated that the early posttraumatic inflammatory response is often accompanied by robust generation of complement activation products [66, 104, 105] . However, up to now, the involvement of the complement cascade in bone and cartilage trauma has only been marginally investigated [130] . In recent years, increased attention has been devoted to the investigation of the role of complement in bone biology and fracture healing [131] . Mesenchymal stem cells as progenitor cells of osteoblasts were shown to express the complement receptors C3aR and C5aR, and the complement regulator molecules, CD55 and CD59 [132] [133] [134] . Moreover, osteoblastic differentiation as a key aspect of bone formation and remodeling induces upregulation of a number of complement-related genes, like C1q, C4, C3aR, properdin, C1-inhibitor (C1-INH) and complement factor H [135] . Pobanz and colleagues reported the expression of a functional C5aR by a human osteoblast-like cell line and detected increased osteoblast IL-6 production after stimulation of these cells with C5a [136] . Furthermore, vitamin D3 has been described to regulate C3 production by murine osteoblastic cells both in vitro and in vivo [137] [138] [139] . Complement C3 was postulated to exhibit a modulating influence on the differentiation of bone marrow cells into osteoclasts [139, 140] . Additional studies pointed out that complement appears to be involved in the transformation of chondral precursors to bone tissue during the enchondral ossification process, involving both the classical and alternative pathway complement activation [141, 142] . Consequently, complement components were hypothesized to be also involved in the inflammatory response after musculoskeletal trauma, and in mediating induction of fracture repair processes [131] . A recent study revealed that the C5aR is expressed in fracture callus by differentiated osteoblast, chondroblast-like cells, and osteoclasts [143] . Since fracture healing is known to be delayed in case of additional trauma-induced injuries, it furthermore remains to be examined if systemic complement generation might be the initiator of this delayed recovery after musculoskeletal trauma [144] .