Journal
ENDOCRINOLOGY
Volume 149, Issue 5, Pages 2051-2061Publisher
ENDOCRINE SOC
DOI: 10.1210/en.2007-1068
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Funding
- NIAMS NIH HHS [AR45433, AR54664, R01 AR045433] Funding Source: Medline
- NIA NIH HHS [AG02331, R01 AG002331, R37 AG002331] Funding Source: Medline
- NIDDK NIH HHS [R01 DK042424, DK042424] Funding Source: Medline
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IGF-binding protein-2 (IGFBP-2) is a 36-kDa protein that binds to the IGFs with high affinity. To determine its role in bone turnover, we compared Igfbp2(-/-) mice with Igfbp2(-/-) colony controls. Igfbp2(-/-) males had shorter femurs and were heavier than controls but were not insulin resistant. Serum IGF-I levels in Igfbp2(-/-) mice were 10% higher than Igfbp2(-/-) controls at 8 wk of age; in males, this was accompanied by a 3-fold increase in hepatic Igfbp3 and Igfbp5 mRNA transcripts compared with Igfbp2(-/-) controls. The skeletal phenotype of the Igfbp2(-/-) mice was gender and compartment specific; Igfbp2(-/-) females had increased cortical thickness with a greater periosteal circumference compared with controls, whereas male Igfbp2(-/-) males had reduced cortical bone area and a 20% reduction in the trabecular bone volume fraction due to thinner trabeculae than Igfbp2(-/-) controls. Serum osteocalcin levels were reduced by nearly 40% in Igfbp2(-/-) males, and in vitro, both CFU- ALP(+) preosteoblasts, and tartrateresistant acid phosphatase- positive osteoclasts were significantly less abundant than in Igfbp2(-/-) male mice. Histomorphometry confirmed fewer osteoblasts and osteoclasts per bone perimeter and reduced bone formation in the Igfbp2(-/-) males. Lysates from both osteoblasts and osteoclasts in the Igfbp2(-/-) males had phosphatase and tensin homolog (PTEN) levels that were significantly higher than Igfbp2(-/-) controls and were suppressed by addition of exogenous IGFBP-2. In summary, there are gender- and compartmentspecific changes in Igfbp2(-/-) mice. IGFBP-2 may regulate bone turnover in both an IGF-I-dependent and -independent manner.
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