Bone Physiopathology Program (BoNetwork)

Heads: Roberto Sitia and Enrico Gherlone

Vision

The skeleton evolved to empower locomotion, shield the neuraxis and the hematopoietic marrow, and amass minerals. Efficient mechanosensing ensures skeletal homeostasis by coordinating the remodeling activity of bone-forming osteoblasts and resorbing osteoclasts. Bone metabolic diseases are frequent and disabling: osteoporosis affects older women and men in every population (35% postmenopausal white women, 19% white men), leading to >1.3 million fractures and 14 billion USD of direct expenditures per year in the US. These figures are rising as life expectancy grows. Pathologic fractures reduce lifespan and cause severe disability. New strategies against osteoporosis and skeletal diseases are needed to promote healthy aging. Understanding how osteoblasts and osteoclasts differentiate and operate, their derangement in bone wasting diseases, and how cancers divert the bone microenvironment will provide targets for osteoporosis and osteolytic cancers. The integrated study of bone biology, stemness and immunity will expand our understanding of skeletal homeostasis and lead to identify new specific therapeutic targets for regenerative medicine.

Goals

The San Raffaele Bone Pathophysiology Program (BoNetwork) aims to integrate basic, translational and clinical research interfacing with bone pathopysiology to generate strong scientific synergies. Specific objectives include: identifying the molecular and cellular bases of bone homeostasis, including determinants of bone mass gain; promoting joint efforts in cartilage and bone engineering; improving bone regeneration in odontoiatrics; identifying potential molecular markers and targets of diseases; establishing robust cellular and animal disease models, and solid core technologies (bone histomorphometry and imaging); providing an attractive interface for pharmaceutical and nutriceutical companies.

Main achievements (updated 2012)

  • Development and preclinical validation of an engineered osteochondral composite for cartilage and osteochondral repair; identification of human cartilage fragments as a source of cells for osteochondral repair; in vitro validation of umbilical cord fragments as a source of cells for orthopaedic tissue engineering.
  • Evaluation of the effects of chronic diseases and associated treatments, particularly HIV and antiretroviral drugs, on skeletal modeling in children/adolescents; identification of genetic variants associated with osteoporosis.
  • Identification of mechanisms conferring therapeutic resistance to multiple myeloma, the prime bone cancer; wide-scope investigation of proteomic and metabolic correlates of myeloma development and progression.
  • Identification and functional characterization of gene variants of the calcium-sensing receptor associated with human disease.
  • Studies of biological features and clinical applications of bone substitutes and dental implants for oral rehabilitation (magnesium-enriched hydroxyapatite nanoparticles, sandblasted and acid etched titanium surfaces); new micro-invasive implant prosthodontics.