RESUMO
Osteoporosis is the most common metabolic bone disorder and its management represents a tremendous public health encumbrance. While several classes of therapeutics have been approved to treat this disease, all are associated with significant adverse effects. An algorithm was developed and utilized to discover potential bioactive peptides, which led to the identification of an osteogenic peptide that mapped to the C-terminal region of the calcitonin receptor and has been named calcitonin receptor fragment peptide (CRFP). In vitro treatment of human mesenchymal stem cells with CRFP resulted in dose-specific effects on both proliferation and osteoblastic differentiation. Similarly, in vitro treatment of rat RCJ3.1C5.18 cells led to dose- and species-specific effects on proliferation. A rat ovariectomy (OVX) model was used to assess the potential efficacy of CRFP in treating osteoporosis. MicroCT analysis of distal femoral samples showed that OVX rats treated with CRFP were significantly protected from losses of 55 % in trabecular bone volume fraction (BVF), 42 % in connectivity density, and 18 % in trabecular thickness in comparison to vehicle-treated controls. MicroCT analyses of vertebrae revealed CRFP to significantly prevent a 25 % reduction in BVF. MicroCT evaluation of femoral and vertebral cortical bone found a significant reduction of 2 % in vertebral bone mineral density. In summary, our in vitro studies indicate that CRFP is both bioactive and osteogenic and our in vivo studies indicate that CRFP is skeletally bioactive. These promising data indicate that further in vitro and in vivo evaluation of CRFP as a new treatment for osteoporosis is warranted.
