Acciones osteogénicas de la proteína relacionada con la parathormona (PTHRP) sobre la regeneración ósea comprometida por glucocorticoides y en la osteoporosis experimental por depleción estrogénica en ratón

Résumé

Abstract Parathyroid hormone-related protein (PTHrP) is an important modulator of bone remodelling and bone formation. High and/or prolonged glucocorticoid (GC) treatment and postmenopausal estrogen depletion lead to bone loss (osteopenia/osteoporosis). In this Doctoral Thesis, we assessed and compared the ability of the N-terminal PTH-like fragment of PTHrP and its PTH-unrelated C-terminal fragment to restore the GC-altered bone regeneration after bone marrow (BM) ablation, and their osteogenic effects on an established model of postmenopausal osteoporosis by ovariectomy (OVX) in mice. Treatment with 3-methylprednisolone in mice showed retardation in bone regeneration after BM ablation, associated with decreased bone formation and vascularization but increased osteoclastogenesis and adipogenesis. We also observed an altered bone structure in the intact femur of these GC-treated mice. These effects were reversed, at least in part, by either PTHrP peptide. In OVX mice, we found an increased osteoclast activity, associated with a decrease in bone formation, which resulted in a loss of bone mass and structure. Both PTHrP fragments reversed these effects, showing anabolic effects in osteopenic bone. The C-terminal fragment of PTHrP also showed antirresorptive features In this setting. In conclusion, these novel findings demonstrate the in vivo osteogenic features of both PTHrP peptides, and suggest they could be envisioned as putative therapies to promote bone regeneration and reverse the alterations in bone mass and structure in osteoporosis.