The effects of prostaglandin E2 in rapidly growing rats: Depressed longitudinal and radial growth and increased metaphyseal hard tissue mass

Ueno, Keisuke; Haba, Teruo; Woodbury, Dixon M.; Price, Paul A.; Anderson, Richard E.; Jee, Webster S. S.

doi:10.1016/8756-3282(85)90311-4

Cited by 108 publications

(29 citation statements)

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“…We and others have previously shown that PGE 2 increases bone formation and mass in intact young, rapidly growing as well as adult rats (Ueno et al 1985, Jee et al 1987 , Jee & Ma 1997, Suponitzki & Weinreb 1998. Recently, PGE 2 was also shown to increase cortical bone formation rate and red/yellow bone marrow ratio in the tibial shaft of intact old male rats (Yao et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…The anabolic effect of systemically administered PGEs was reported in many species including young (Ueno et al 1985, Jee et al 1987, Suponitzki & Weinreb 1998 and adult (Ke et al 1991 rats as well as humans (Ueda et al 1980, Jorgensen et al 1988. Detailed analysis of the effects of PGE 2 in these growing rats showed that it increases bone formation and bone mass mainly by increasing the number of osteoblasts present on bone surfaces and by inducing the production of new bone.…”

Section: Introductionmentioning

confidence: 99%

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Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Keila¹,

Kelner²,

Weinreb³

2001

Journal of Endocrinology

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Prostaglandin E 2 (PGE 2 ) has been shown to exert a bone anabolic effect in young and adult rats. In this study we tested whether it possesses a similar effect on bone formation and bone mass in aging rats. Fifteen-month-old rats were injected daily with either PGE 2 at 5 mg/kg or vehicle for 14 days. PGE 2 treatment stimulated the rate of cancellous bone formation (a 5·5-fold increase in bone formation rate), measured by the incorporation of calcein into bone-forming surfaces at the tibial proximal metaphysis. This effect resulted in increased cancellous bone area (+54%) at the same site. Since PGE 2 treatment resulted in a much higher proportion of bone surface undergoing bone formation and thus lined with osteoblasts, we tested the hypothesis that PGE 2 stimulates osteoblast differentiation from bone marrow precursor cells both in vivo and in vitro. We found that ex vivo cultures of bone marrow stromal cells from rats injected for 2 weeks with PGE 2 at 5 mg/kg per day yielded more (4-fold) mineralized nodules and exhibited a greater (by 30-40%) alkaline phosphatase activity compared with cultures from vehicle-injected rats, attesting to a stimulation of osteoblastic differentiation by PGE 2 .We also compared the osteogenic capacity of bone marrow from aging (15-month-old) versus young (5-week-old) rats and its regulation by PGE 2 in vitro. Bone marrow stromal cell cultures from aging rats exhibited a greatly diminished osteogenic capacity, reflected in reduced nodule formation (6% of young animals) and lower alkaline phosphatase activity (60% of young animals). However, these parameters could be stimulated in both groups of animals by incubation with 10-100 nM PGE 2 . The magnitude of this stimulation was greater in cultures from aging rats (+550% vs +70% in nodule formation of aging compared with young rats).In conclusion, we demonstrate here that PGE 2 exerts a bone anabolic effect in aging rats, similar to the effect we and others have reported in young, growing rats. The PGE 2 -stimulated bone formation, which augments bone mass, most likely results from recruitment of osteoblasts from their bone marrow stromal precursors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Keila¹,

Kelner²,

Weinreb³

2001

Journal of Endocrinology

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“…This dose is within the range known to be anabolic in rats (Ueno et al 1985, Jee et al 1987, 1992, Suponitzki & Weinreb 1998. Total RNA was extracted from the tibial metaphysis using a guanidinium isothiocyanate-phenol-chloroform method (Chomczynski & Sacchi 1987), after pulverizing frozen bone samples by a tissue homogenizer.…”

Section: Northern Blot Analysismentioning

confidence: 95%

“…It is now established that PGE 2 -induced bone formation results primarily from the appearance of new osteoblasts and production of new bone. Previously, others and ourselves have reported that PGE 2 is anabolic in young and aging rats (Ueno et al 1985, Jee et al 1987, 1992, Suponitzki & Weinreb 1998). In addition, we have published a detailed analysis of the effects of PGE 2 and have clarified some aspects of the mechanisms involved in the actions of PGE 2 : induction of early response genes (Weinreb et al 1997a), stimulation of osteoblast differentiation from bone marrow osteoprogenitors (Weinreb et al 1997b, Keila et al 2001) and involvement of the cAMP signaling pathway and of the EP 4 receptor (Weinreb et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cyclo-oxigenase-2 activity does not abolish the anabolic effect of prostaglandin E2 in vivo or in vitro

Weinreb

Kelner²,

Keila³

2002

Journal of Endocrinology

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It was previously reported that the expression of cyclooxigenase-2 (COX-2) is induced by prostaglandin E 2 (PGE 2 ) in vitro in an osteogenic cell line and organ culture, suggesting an autoamplification mechanism. In this study, we first tested whether this phenomenon also occurs in bone tissue in vivo and found that a single anabolic dose of PGE 2 (5 mg/kg) induced (between 30 and 120 min) in rat tibiae, an increase in the mRNA level of COX-2 (2·5-to 9-fold) but not that of COX-1. Secondly, to test whether COX-2 activity in generating endogenous prostaglandins (PGs) is required for the in vivo anabolic properties of PGE 2 , young male rats were injected daily with either vehicle (8% ethanol) or 5 mg/kg PGE 2 for 21 days. PGE 2 -injected rats received, 45 min prior to PGE 2 , either dimethyl sulphoxide (as vehicle) or one of two doses of NS-398, a selective COX-2 inhibitor: a low dose (3 mg/kg) or a high dose (10 mg/kg). PGE 2 increased bone formation (measured as cancellous mineralizing surface, mineral apposition rate and bone formation rate) and bone mass (measured as cancellous bone area and surface and cortical width). None of these increases was suppressed by pre-administration of NS-398. In contrast, the high dose of NS-398 effectively suppressed an increase in rat hind-paw volume induced by a local carrageenan injection. Furthermore, since COX-2 inactivation may affect PG receptor expression, we found that preadministration of NS-398 did not abolish the induction in EP 4 receptor mRNA levels, caused by PGE 2 in rat bone tissue. For in vitro testing, rat femoral bone marrow stromal cell cultures were initiated and were incubated in the absence or presence of PGE 2 at 100 nM (as an inducer) and with increasing concentrations of NS-398 (10 8 M to 10 5 M) for 21 days, after which time mineralized (Von-Kossa positive) nodules were counted. PGE 2 increased nodule formation as previously reported; however, NS-398 reduced nodule formation in both control and PGE 2 -treated cultures to the same extent. We conclude that while the level of COX-2 mRNA is increased in vivo by administration of PGE 2 , inhibition of its activity (i.e. generation of endogenous PGs) does not abolish the anabolic effect of PGE 2 .

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“…Upon reviewing the literature, we found that PGE2 has a stimulatory effect in high doses on the division of prechondroblasts (Falconer et al 1980) and on the formation of fracture callus (Juhn et al 1989). Further, PGE2 and PGEl increase endosteal bone growth in infants and bone formation in dogs after rib fractures (Ueda et al 1980, Ueno et al 1985, Shih and Norrdin 1986, High 1987, Norrdin and Shih 1988. PGE2 might therefore be important in the initiation of bone healing.…”

Section: Discussionmentioning

confidence: 99%

Release of prostaglandins from bone and muscle after femoral osteotomy in rats

Wittenberg

1991

Acta Orthopaedica Scandinavica

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The effects of prostaglandin E2 in rapidly growing rats: Depressed longitudinal and radial growth and increased metaphyseal hard tissue mass

Cited by 108 publications

References 50 publications

Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Inhibition of cyclo-oxigenase-2 activity does not abolish the anabolic effect of prostaglandin E2 in vivo or in vitro

Release of prostaglandins from bone and muscle after femoral osteotomy in rats

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