Spaceflight Effects On Cultured Embryonic Chick Bone Cells
biomechanics; bone adaptation; collagen; differentiation; Endocrinology & Metabolism; in-vitro; mechanical strain; messenger-rna expression; microgravity; osteoblast; osteoblasts; osteopontin; restriction; signal-transduction; space-flight
A model calcifying system of primary osteoblast cell cultures derived from normal embryonic chicken calvaria has been flown aboard the shuttle, Endeavour, during the National Aeronautics and Space Administration (NASA) mission STS-59 (April 9-20, 1994) to characterize unloading and other spaceflight effects on the bone cells. Aliquots of cells (similar to 7 x 10(6)) grown in Dulbecco's modified Eagle's medium (DMEM) + 10% fetal bovine serum (FBS) were mixed with microcarrier beads, inoculated into cartridge culture units of artificial hollow fiber capillaries, and carried on the shuttle. To promote cell differentiation, cartridge media were supplemented with 12.5 mu g/ml ascorbate and 10 mM P-glycerophosphate for varying time periods before and during Right. Four cartridges contained cells from 17-day-old embryos grown for 5 days in the presence of ascorbate prior to launch (defined as flight cells committed to the osteoblastic lineage) and four cartridges supported cells from 14-day-old embryos grown for 10 days with ascorbate before launch (uncommitted flight cells). Eight cartridges prepared in the same manner were maintained under normal gravity throughout the Right (control cells) and four additional identical cartridges under normal gravity were terminated on the day of launch (basal cells). From shuttle launch to landing, all cartridges were contained in closed hardware units maintaining 5% CO2, 37 degrees C, and media delivery at a rate of similar to 1.5 ml/6 h. During day 3 and day 5 of flight, duplicate aliquots of conditioned media and accumulated cell products were collected in both the Right and the control hardware units. At the mission end, comparisons among Right, basal, and control samples were made in cell metabolism gene expression for type I collagen and osteocalcin, and ultrastructure. Both committed and uncommitted flight cells were metabolically active, as measured by glucose uptake and lactate production, at approximately the same statistical levels as control counterparts. Flight cells elaborated a less extensive extracellular matrix, evidenced by a reduced collagen gene expression and collagen protein appearance compared with controls. Osteocalcin was expressed by all cells, a result indicating progressive differentiation of both flight and control osteoblasts, but its message levels also were reduced in flight cells compared with ground samples. This finding suggested that osteoblasts subjected to flight followed a slower progression toward a differentiated function. The summary of data indicates that spaceflight, including microgravity exposure, demonstrably affects bone cells by down-regulating type I collagen and osteocalcin gene expression and thereby inhibiting expression of the osteogenic phenotype notably by committed osteoblasts. The information is important for insight into the response of bone cells to changes of gravity and of force in general.
Landis W J; Hodgens K J; Block D; Toma C D; Gerstenfeld L C
Journal of Bone and Mineral Research
2000
2000-06
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1359/jbmr.2000.15.6.1099" target="_blank" rel="noreferrer noopener">10.1359/jbmr.2000.15.6.1099</a>
Invited review: Role of mechanophysiology in aging of ECM: effects of changes in mechanochemical transduction
age; apoptosis; collagen; connective tissue; dermal fibroblasts; expansion; extracellular-matrix; gene-expression; growth-factor responsiveness; guinea-pig; human articular chondrocytes; mechanical forces; mechanical strain; phosphorelay system; Physiology; silicone implant; skin; Sport Sciences; tissue
Mechanical forces play a role in the development and evolution of extracellular matrices (ECMs) found in connective tissue. Gravitational forces acting on mammalian tissues increase the net muscle forces required for movement of vertebrates. As body mass increases during development, musculoskeletal tissues and other ECMs are able to adapt their size to meet the increased mechanical requirements. However, the control mechanisms that allow for rapid growth in tissue size during development are altered during maturation and aging. The purpose of this mini-review is to examine the relationship between mechanical loading and cellular events that are associated with downregulation of mechanochemical transduction, which appears to contribute to aging of connective tissue. These changes result from decreases in growth factor and hormone levels, as well as decreased activation of the phosphorelay system that controls cell division, gene expression, and protein synthesis. Studies pertaining to the interactions among mechanical forces, growth factors, hormones, and their receptors will better define the relationship between mechanochemical transduction processes and cellular behavior in aging tissues.
Silver F H; DeVore D; Siperko L M
Journal of Applied Physiology
2003
2003-11
Journal Article
<a href="http://doi.org/10.1152/japplphysiol.00429.2003" target="_blank" rel="noreferrer noopener">10.1152/japplphysiol.00429.2003</a>