Cellular patterns of insulin-like growth factor system gene expression in murine chondrogenesis and osteogenesis.
In situ hybridization histochemistry was used to map cellular patterns of gene expression for the insulin-like growth factor (IGF) system in developing murine skeleton from embryonic day 15 (E15) through postnatal day 25 (P25). IGF-I receptor and IGF-II receptor messenger RNAs (mRNAs) are both selectively concentrated in developing chondrocytes and osteoblasts. IGF-II and IGF-binding protein-5 and -6(IGFBP-5 and -6) mRNAs are abundant in mesenchymal condensations and chondroblasts on E15. Chondrocyte IGF-II mRNA levels remain high, but IGFBP-5 and -6 mRNAs decline significantly as cartilage matures. Low levels of IGFBP-6 mRNA are detected in postnatal chondrocytes up to at least P25, but IGFBP-5 mRNA is no longer detected in chondrocytes after E18. IGF-I and IGFBP-2, -3, and -4 mRNAs are detected in surrounding mesenchymal tissue, but are not detected in mesenchymal condensations or chondrocytes at any stage of development. IGFBP-3 mRNA is localized in sprouting capillaries invading the perichondrium and periosteum throughout development. IGF-I, IGF-II, and IGFBP-2, -4, -5, and -6 mRNAs are detected in osteoblasts localized in zones of endochondral ossification from E18 to at least P25. IGFBP-1 mRNA is not detected in cartilage or bone cells at any stage of development. These data confirm the recent report by Shinar et al. that IGF-II, but not IGF-I, mRNA is detected in rat chondrocytes in vivo and show that this pattern also applies to the mouse. The present study demonstrates, for the first time, the cell-specific patterns of IGF-I and -II receptor and IGFBP-2 to -6 gene expression during the processes of chondro- and osteogenesis in vivo. Interestingly, IGF-II, both IGF receptors, and IGFBP-5 and -6 are simultaneously coexpressed in chondrocyte precursors early in skeletal development, suggesting functional interactions between these specific factors in chondrogenesis. Both IGFs, both IGF receptors, and IGFBP-2, -4, -5, and -6 are all expressed in osteoblasts, providing evidence for potential local interactions between these IGF system components in osteogenesis. Thus, 9 of 10 known components of the IGF system demonstrate dynamic cell-specific patterns of gene expression during chondro- and osteogenesis, supporting the view that the IGF system has a complex and integral role within the developing skeleton.
Wang
E
E
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Wang
J
J
Chin
E
E
Zhou
J
J
Bondy
C A
CA
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002356:Cartilage / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D010012:Osteogenesis / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics; D013002:Somatomedins / Q000235:genetics*
D002352:Carrier Proteins; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1