title: Surface microtopography modulates sealing zone development in osteoclasts cultured on bone.
abstract: Bone homeostasis is continuously regulated by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between these two cell populations leads to pathological bone diseases such as osteoporosis and osteopetrosis. Osteoclast functionality relies on the formation of sealing zone (SZ) rings that define the resorption lacuna. It is commonly assumed that the structure and dynamic properties of the SZ depend on the physical and chemical properties of the substrate. Considering the unique complex structure of native bone, elucidation of the relevant parameters affecting SZ formation and stability is challenging. In this study, we examined in detail the dynamic response of the SZ to the microtopography of devitalized bone surfaces, taken from the same area in cattle femur. We show that there is a significant enrichment in large and stable SZs (diameter larger than 14 µm; lifespan of hours) in cells cultured on rough bone surfaces, compared with small and fast turning over SZ rings (diameter below 7 µm; lifespan approx. 7 min) formed on smooth bone surfaces. Based on these results, we propose that the surface roughness of the physiologically relevant substrate of osteoclasts, namely bone, affects primarily the local stability of growing SZs.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel.|Department of Molecular Cell Biology, Weizmann Institute of Science, Wolfson Building for Biological Research, Room 618, 234 Herzl Street, 7610001 Rehovot, Israel.
authors.forename: Michal
authors.identifier: 0000-0002-0782-5991
authors.initials: M
authors.lastname: Shemesh
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Lia
authors.initials: L
authors.lastname: Addadi
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Wolfson Building for Biological Research, Room 618, 234 Herzl Street, 7610001 Rehovot, Israel benny.geiger@weizmann.ac.il.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Geiger
mesh_terms: D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D005269:Femur / Q000737:chemistry*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D013499:Surface Properties
keywords: actin dynamics; atomic force microscopy; bone roughness