Saturday, April 25, 2009


Altered bone development and turnover in transgenic mice over-expressing lipocalin-2 in bone.

"LCN2[Lipocalin-2] was expressed during osteoblast differentiation and we generated transgenic (Tg) mice over-expressing LCN2{under the Col1a1 promoter} in bone. Tg mice were smaller and presented bone microarchitectural changes in both endochondral and intramembranous bones. In particular, Tg bones displayed a thinner layer of cortical bone and a decreased trabecular number. Osteoblast bone matrix deposition was reduced and osteoblast differentiation was slowed-down. Differences were also observed in the growth plate of young transgenic mice where chondrocyte displayed a more immature phenotype and a lower proliferation rate. In bone marrow cell cultures from transgenic mice, the number of osteoclast progenitors was increased whereas in vivo it was increased the number of mature osteoclasts expressing tartrate resistant acid phosphatase (TRAP). Finally, while osteoprotegerin (OPG) levels remained unchanged, the expression of the conventional Receptor Activator of Nuclear factor-κB Ligand (RANKL) and of the IL-6 was enhanced in Tg mice."

Would decreasing LCN2 levels increase height?

"LCN2 binds iron influencing cellular proliferation rate."<-Maybe increasing the levels of iron can counteract high LCN2 levels?

"When added to cultures of the ATDC5 cell line, [LCN2] affected chondrocyte proliferation and differentiation"

"Both Lcn2 mRNA and protein expression were negligible in undifferentiated cells (T0)"

Femur length in transgenic mice was shorter than wild type starting at three weeks.  In transgenic mice there was higher staining for Type II Collagen and lower staining for Type X collagen.

"LCN2 is expressed in chondrocytes during endochondral ossification"

"bones of Tg mice grew at a slower rate than Wt bones."<-So only rate may have been affected and not adult height.

"transgenic mice over-expressing IL-6 were smaller"

According to Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis., LCN2 KO mice have higher levels of iron.

LCN2 is a gene that is likely required to be at optimal levels for maximal height growth.

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