Sunday, July 3, 2011

anxa5

Here's some details about the Entheses.
Annexin A5 involvement in bone overgrowth at the enthesis.

"Little is known about the molecular mechanisms of enthesis formation in mature animals. Here, we report that annexin A5 (Anxa5) plays a critical role in the regulation of bone ridge outgrowth at the entheses. We found that Anxa5 is highly expressed in the entheses of postnatal and adult mice. In Anxa5-deficient (Anxa5-/- ) mice, the sizes of bone ridge outgrowths at the entheses of the tibiae and femur were increased after 7 weeks of age. Bone overgrowth was not observed at the fibrous enthesis where the fibrocartilage layer does not exist. More ALP-expressing cells were observed in the fibrocartilage layer in Anxa5-/- mice than in wild-type (WT) mice. Calcein and Alizarin Red double labeling revealed more mineralized areas in Anxa5-/- mice than WT mice. To examine the effects of mechanical forces, we performed tenotomy in which transmission of contractile forces by the tibial muscle was impaired by surgical muscle release. In tenotomized mice, bone overgrowth at the enthesis in Anxa5-/- mice was decreased to a level comparable to that in WT mice at 8 weeks after the operation. The tail-suspended mice also showed a decrease in bone overgrowth to similar levels in Anxa5-/- and WT mice at 8 weeks after hindlimb unloading. These results suggest that bone overgrowth at the enthesis requires mechanical forces. We further examined effects of AnxaA5 gene knockdown (KD) in primary cultures of osteoblasts, chondrocytes, and tenocytes in vitro. AnxaA5 KD increased ALP expression in tenocytes and chondrocytes but not in osteoblasts, suggesting that increased ALP activity in the fibrocartilaginous tissue in AnxaA5 KO mice is directly caused by Anxa5 deletion in tenocytes or fibrocartilage cells. These data indicate that Anxa5 prevents bone overgrowth at the enthesis, whose formation is mediated through mechanical forces and modulating expression of mineralization regulators."

"Tendons and ligaments are connected to bones through a specialized transitional
tissue called the enthesis"

"Anxa5 mediates the Ca2+ influx into matrix vesicles secreted from
hypertrophic chondrocytes in the growth plate by interacting with extracellular type II and
type X collagens, thereby initiating cartilage calcification"

"the Anxa5–/– mice were viable and fertile, and showed no significant differences in body weight and longitudinal tibial bone length until 40 weeks of age when compared to Anxa5+/+ and Anxa5+/– mice. However, under a binocular microscope, we found that several portions of tendon insertions to the bones were projected abnormally in the Anxa5-/- mice compared to the wild-type mice. For example, the bone ridge at the insertion of the tibialis anterior muscle, and that at the trochanter
tertius of the proximal femur was prominent in the Anxa5-/- mice "

"To assess whether the localized phenotype at the entheses is caused by changes in the
genetically regulated pattern formation of bone outlines or involves mechanical force-driven
local growth of fibrocartilaginous tissues, we used tenotomy to eliminate tibial muscle
contractile force transmission. Microscopic observation revealed that bone ridge overgrowth at the enthesis was suppressed at tenotomized sites to a similar extent in Anxa5–/– and Anxa5+/+ mice "

" AnxaA5KD in chondrocytes resulted in up-regulation of Sox9, whereas it increased Scx and Tnmd
expression in tenocytes , suggesting that AnxaA5KD promotes chondrocyte and tenocyte
differentiation. AnxaA5KD in osteoblasts resulted in decreased Runx2 and
osteopontin expression, suggesting that AnxaA5KD inhibits osteoblastic differentiation "

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