Role for parathyroid hormone in mechanical responsiveness of rat bone

1998 ◽  
Vol 274 (1) ◽  
pp. E146-E154 ◽  
Author(s):  
J. W. M. Chow ◽  
S. Fox ◽  
C. J. Jagger ◽  
T. J. Chambers

We investigated the relationship between parathyroid hormone (PTH) and mechanical stimulation in mechanically induced osteogenesis. In normal rats, mechanical stimulation of the eighth caudal vertebra induced an osteogenic response. This was augmented by a single injection of human PTH-(1—34) 30–45 min before loading. No osteogenic response was seen in thyroparathyroidectomized (TPTX) rats; the osteogenic response was restored by a single injection of PTH before stimulation, suggesting that physiological levels of PTH are necessary for the mechanical responsiveness of bone. c- fosexpression was detected only in the osteocytes of those rats that were both mechanically stimulated and given PTH. This suggests that PTH supports mechanically induced osteogenesis by sensitizing either the strain-sensing mechanism itself or early responses of bone to strain-generated signals. The osteogenic response was not augmented by two further daily injections of PTH and was not seen in TPTX rats in which PTH administration was started 3 days after loading. These results reveal a major role for PTH in the mechanical responsiveness of rat bone.

1967 ◽  
Vol 13 (7) ◽  
pp. 795-803
Author(s):  
Fred S. Shults ◽  
John M. Woodward

Studies of differences in hydrolase activity of peritoneal mononuclear leucocytes from normal rats and rats given three injections of killed Francisella tularensis vaccine demonstrated increases of 37–69% in ribonuclease, deoxyribonuclease, and acid phosphatase in lysates of cells obtained from vaccinated animals. No deviation from normal was observed for B-glucuronidase, alkaline phosphatase, or cathepsin. Following a single injection of vaccine the activity of ribonuclease, deoxyribonuclease, and acid phosphatase decreased slightly and then increased, reaching a maximum of 96 h and returning to normal levels after 30 d. Stimulation of the animals with a second injection of vaccine at 96 h resulted in an immediate and pronounced depression in activity of deoxyribonuclease and acid phosphatase which also was followed by an increase similar to that observed initially. Analysis of the various leucocytic fractions revealed 52.2–56.4% of the total enzymatic activity to be associated with the cytoplasmic granules.


1996 ◽  
Vol 270 (6) ◽  
pp. E937-E945 ◽  
Author(s):  
J. M. Lean ◽  
A. G. Mackay ◽  
J. W. Chow ◽  
T. J. Chambers

We analyzed the expression, during the osteogenic response of bone to mechanical stimulation, of insulin-like growth factor I (IGF-I), a growth factor implicated in bone formation, and c-fos, a protooncogene in which disordered regulation specifically affects bone. Both genes were strongly expressed in osteocytes of mechanically stimulated but not control bones within 30 min of the osteogenic stimulus. IGF-I mRNA expression increased up to 6 h, was restricted to osteocytes, and was strongly suppressed by indomethacin. Although early IGF-I mRNA expression was resistant to cycloheximide, there was a degree of suppression after 6 h, raising the possibility that IGF-I expression might be prolonged by autocrine mechanisms. c-fos mRNA was increased both in osteocytes and on bone surfaces. At both sites, c-fos expression was transient, prolonged by cycloheximide, and was strongly stimulated even in the presence of indomethacin. Thus osteocytes respond to mechanical stimulation with immediate prolonged expression of IGF-I and immediate transient expression of c-fos, implicating osteocytes in the osteogenic response to mechanical stimulation. Moreover, the different spatial distribution and indomethacin sensitivity of c-fos and IGF-I gene expression suggest that at least two signaling pathways are activated in osteocytes during this process.


1989 ◽  
Vol 61 (1) ◽  
pp. 138-148 ◽  
Author(s):  
H. Hirata ◽  
B. H. Pubols

1. The extracellular activity of 45 antidromically identified spinocervical tract (SCT) neurons responsive to light mechanical stimulation of the glabrous surfaces of the forepaw was examined in raccoons anesthetized with pentobarbital sodium. An additional seven neurons had peripheral receptive fields (RFs) located on hairy skin of the forelimb, and three had deep RFs. 2. All recording sites were histologically verified as falling within Rexed's laminae III and IV in spinal cord segments C6-T1. Antidromic conduction velocities of the 55 neurons ranged between 8.3 and 64.2 m/s. 3. Units with glabrous skin RFs were classified according to their response to a maintained mechanical stimulus as either rapidly adapting (n = 39) or slowly adapting (n = 6). Of 11 cells tested, 2 displayed enhanced responses to noxious stimuli and were classed as multireceptive. 4. RF areas were significantly smaller on digits (range = 0.4-45.0 mm2) than on palm pads (range = 5.6-76.0 mm2), and comparable in size to RF areas previously reported in raccoon cuneate nuclear cells (32). 5. RA neurons fell into three distinct categories with respect to the relationship between instantaneous spike frequency during displacement ramp stimulation, and ramp velocity, steep functions (as defined by the value of power function exponents), flat functions, and discontinuous functions; SA neurons fell into two categories, continuous, and discontinuous. 6. The results, in conjunction with those of previous studies, lead to two major conclusions: 1) raccoon and primate spinocervicothalamic systems are more similar to each other than either is to that of the cat and 2) the ability of the raccoon SCT to convey information from the glabrous skin of the forepaw regarding characteristics of light mechanical stimuli is at least as precise as that of neurons of the dorsal column-medial lemniscal system.


1993 ◽  
Vol 265 (2) ◽  
pp. E340-E347 ◽  
Author(s):  
J. W. Chow ◽  
C. J. Jagger ◽  
T. J. Chambers

We have recently developed an experimental model in which pins, inserted into the 7th and 9th caudal vertebrae of 13-wk-old rats, are used to load the 8th caudal vertebra in compression. We have now applied this model to assess the responsiveness of rat cancellous bone to mechanical stimulation. We found that daily exposure to loads that induce strains similar to those observed in bone during relatively gentle physical activity, for 30 cycles/day, increased the rate of lamellar bone formation on cancellous surfaces by up to 140-fold. Bone formation rate showed a highly significant (P < 0.0001) correlation with the number of days for which the bones were loaded and with the size of the load. A single loading episode of 300 cycles, representing a 10-min period of loading, increased bone formation to 24 times that in nonloaded controls. Indexes of bone resorption were essentially the inverse of the bone formation parameters. These experiments show that rat cancellous bone is exquisitely sensitive to mechanical stimulation and suggest that the mechanical environment is a major determinant of the physiological behavior of mammalian cancellous bone.


2001 ◽  
Vol 120 (5) ◽  
pp. A83-A83
Author(s):  
M KIM ◽  
N JAVED ◽  
F CHRISTOFI ◽  
H COOKE

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