title: The active role of osteoporosis in the interaction between osteoblasts and bone metastases.
abstract: BACKGROUND
  To minimize the severity of bone metastases and to delay their onset, it is important to analyze the underlying biological mechanisms. The present study focused on the link between OP and metastatic cells, with particular attention to osteoblast behavior.
  
  
  METHODS
  Osteoblasts (OB) were isolated from the trabecular bone of iliac crest of healthy (SHAM) and ovariectomized (OVX) adult female rats and co-cultured with MRMT-1 rat breast carcinoma cells as conditioned medium (CM) or alone (CTR) for 24h, 7 and 14 days and tested for cell viability, morphology and synthetic activity, i.e. C-terminal procollagen type I, alkaline phosphatase, osteoprotegerin, receptor activator for nuclear factor KB ligand and interleukin-8.
  
  
  RESULTS
  Osteoblast morphology showed a reduced organization in the OVX group, in particular in the CM condition. Conversely, the analysis of cell viability revealed significantly higher values in the OVXCM group with respect to the SHAMCM group at all experimental times, whereas the OVXCTR group had significantly lower values at 7 and 14 days in comparison to those of the SHAM group. ALP release was significantly lower in the CM condition than that of CTR at all timepoints, and so was procollagen type I at 7 and 14 days. The RANKL/OPG ratio showed significantly higher values in OVX osteoblasts in comparison with those of the SHAM group, both in CTR and in CM conditions at each experimental time. Finally, OVXCM showed significantly higher values of IL-8 than those of SHAMCM at 7 and 14 days.
  
  
  CONCLUSIONS
  The results clearly indicate an influence of the metastatic cells on the osteoblastic physiology at different levels: morphology, viability, release of typical proteins, and also IL-8 as a proinflammatory cytokine, especially marked by osteoporosis. Further investigations might highlight the relationship between osteoblasts and breast cancer cells, which might be useful to improve common drugs used against osteoporosis and bone metastases, by enhancing the bone deposition/tumor progression ratio.
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy; Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy. Electronic address: stefania.pagani@ior.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pagani
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy; Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy; Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giavaresi
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Salamanna
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Borsari
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications / Q000473:pathology*; D001943:Breast Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010024:Osteoporosis / Q000209:etiology*; D010052:Ovariectomy; D051381:Rats
keywords: Breast cancer cells; Metastasis; Osteoblasts; Osteoporosis