title: Three-Dimensional in Vitro Model to Study Osteobiology and Osteopathology.
abstract: The bone is an amazing organ that grows and remodels itself over a lifetime. It is generally accepted that bone sculpting in response to stress and force is carried out by groups of cells contained within bone multicellular units that are coordinated to degrade existing bone and form new bone. Because of the nature of bone and the extensiveness of the skeleton, it is difficult to study bone remodeling in vivo. On the other hand, because the bone contains a complex environment of many cell types, is it possible to study bone remodeling in vitro? We propose that one can at minimum study the interaction between osteoblasts (bone formation) and osteoclasts (bone degradation) in a three dimensional (3D) "bioreactor". Furthermore, one can add bone degrading metastatic cancer cells, and study how they contribute to and take part in the bone degradation process. We have primarily cultured and differentiated MC3T3-E1 osteoblasts for long periods (2-10 months) before addition of bone marrow osteoclasts and/or metastatic (MDA-MB-231), metastasis suppressed (MDA-MB-231BRMS1) or non-metastatic (MCF-7) breast cancer cells. In the co-culture of osteoblasts and osteoclasts there was clear evidence of matrix degradation. Loss of matrix was also evident after co-culture with metastatic breast cancer cells. Tri-culture permitted an evaluation of the interaction of the three cell types. The 3D system holds promise for further studies of cancer dormancy, hormone, and cytokine effects and matrix manipulation.
authors.affiliation: The Huck Institute of Life Sciences, Penn State University, University Park, Pennsylvania.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnan
authors.affiliation: Department of Materials Science and Engineering, Penn State University, University Park, Pennsylvania.
authors.forename: Erwin A
authors.initials: EA
authors.lastname: Vogler
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, 16802, Pennsylvania.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Mastro
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000235:genetics*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned
keywords: 3D CULTURE UNIT; BONE REMODELING; METASTATIC CANCER; OSTEOBLASTS; OSTEOCLASTS