title: Osteoblast hydraulic conductivity is regulated by calcitonin and parathyroid hormone.
abstract: It is our hypothesis that osteoblasts play a major role in regulating bone (re)modeling by regulating interstitial fluid (ISF) flow through individual bone compartments. We hypothesize that osteoblasts of the blood-bone membrane lining the bone surfaces are capable of regulating transosseous fluid flow. This regulatory function of the osteoblasts was tested in vitro by culturing a layer of rat calvarial osteoblasts on porous membranes. Such a layer of osteoblasts subjected to 7.3 mm Hg of hydrostatic pressure posed a significant resistance to fluid flow across the cell layer similar in magnitude to the resistance posed by endothelial monolayers in vitro. The hydraulic conductivity, the volumetric fluid flux per unit pressure drop, of the osteoblast layer was altered in response to certain hormones. Hydraulic conductivity decreased approximately 40% in response to 33 nM parathyroid hormone, while it exhibited biphasic behavior in response to calcitonin: increased 40% in response to 100 nM calcitonin and decreased 40% in response to 1000 nM calcitonin. Further, activation of adenylate cyclase by forskolin dramatically increased the hydraulic conductivity, while elevation of intracellular calcium, [Ca2+]i, by the calcium ionophore A23187 initially decreased the hydraulic conductivity at 5 minutes before increasing conductivity by 30 minutes. These results suggest that cyclic adenosine monophosphate (cAMP) and [Ca2+]i may mediate changes in the osteoblast hydraulic conductivity. The increase in hydraulic conductivity in response to 100 nM calcitonin and the decrease in response to PTH suggest that the stimulatory and inhibitory effects on bone formation of calcitonin and parathyroid hormone, respectively, may be due in part to alterations in bone fluid flow.
authors.affiliation: Department of Chemical Engineering, Pennsylvania State University, University Park, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Hillsley
authors.forename: J A
authors.initials: JA
authors.lastname: Frangos
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D001826:Body Fluids / Q000187:drug effects / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002116:Calcitonin / Q000494:pharmacology* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000502:physiology; D051381:Rats
chemical_list: D010281:Parathyroid Hormone; D002116:Calcitonin; D000242:Cyclic AMP; D002118:Calcium