Insulin-like growth factor 1 and parathyroid hormone effects on the growth of fetal rat metatarsal bones cultured in serum-free medium.
Insulin-like growth factor 1 (IGF-1) has roles in bone growth, and parathyroid hormone (PTH) is suspected of having effects on bone, perhaps mediated by IGF-1. The purpose of this study was to determine the individual and combined effect of PTH and IGF-1 on fetal long bone metabolism. Three medial metatarsal bones were dissected from Sprague-Dawley rat fetuses harvested at the 19th day of gestation, then grown in serum-free MEM. IGF-1 (group II) or PTH (group PP) were added at the dose of 100 ng/ml for 8 days. In a third group (PI), bones were preincubated for 4 days with PTH followed by a 4-day incubation with IGF-1. Both hormones stimulated endochondral (longitudinal) growth, the highest effect was observed with IGF-1 (II: 3.11 +/- 0.06 vs. 2.16 +/- 0.08 mm in controls). The length elicited by the PI treatment ranged between those measured with IGF-1 (II) and PTH (PP) given alone (PI: 2.80 +/- 0.04 mm; PP: 2.57 +/- 0.06 mm). In addition, both hormones enhanced periosteal growth (endomembranous ossification), as measured by the width of bones (II: 0.39 +/- 0.02 mm; PP: 0.34 +/- 0.02 mm; PI: 0.38 +/- 0.02 vs. 0.29 +/- 0.01 mm in controls). On the other hand, IGF-1 but not PTH caused a significant increase in 35S incorporation (as an indicator of sulfated proteoglycan synthesis in cartilage (percent of incorporating activity; II: 0.18 +/- 0.04%; PI: 0.09 +/- 0.01 vs. 0.03 +/- 0.01% in controls). Nevertheless, both IGF-1 and PTH enhanced osteoblastic activity as shown by increased alkaline phosphatase activity in treated bones (II: 1.18 +/- 0.00 mumol/bone; PP: 0.50 +/- 0.00 vs. 0.28 +/- 0.00 mumol/bone). In conclusion, IGF-1 had the greatest effects on growth in bone length (endochondral osteogenesis) and bone width (intramembranous osteogenesis) and appeared to stimulate both chondrogenesis and osteogenesis. It also increased growth but appeared to have greater effects on osteogenesis than on chondrogenesis. Pretreatment with IGF-1 followed by PTH produced effects that were intermediate between the groups treated with IGF-1 and PTH alone.
Coxam
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Radiobiology Division, University of Utah, Salt Lake City, USA.
Miller
M A
MA
Bowman
B M
BM
Qi
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D
Miller
S C
SC
D000818:Animals; D015519:Bone Density; D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005333:Fetus; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008684:Metatarsus / Q000196:embryology*; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats / Q000196:embryology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D010281:Parathyroid Hormone; D007334:Insulin-Like Growth Factor I; D013936:Thymidine