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Seminars: October 16-17, 2014 - Prof. Lynda Bonewald


October 16-17, 2014

Prof. Lynda Bonewald

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“The Amazing Osteocyte-Conductor of Bone Remodeling””
The osteocyte was once thought to be a passive cell, acting as a placeholder
in bone.  Several researchers had postulated that this cell  functioned as a
mechanosensor based on the distinctive dendritic morphology.  Few envisioned
this cell to have the capacity to send signals to both osteoclasts and
osteoblasts to remodel or maintain bone mass.  Signals are being elucidated
and include RANKL a stimulator of osteoclast activity,  sclerostin, an
inhibitor of osteoblast activity, and prostaglandin, a stimulator of
osteoblast activity.  These cells also appear to have the capacity to remove
and replace their perilacunar matrix using some of the repertoire of
osteoclast genes.   In summary, these cells far from being passive
placeholders are multifunctional.

"“The Essential Role of b-Catenin in Osteocyte Mechanosensation”"

The b-Catenin signaling pathway clearly plays an essential role in growth
and development.  Targeted deletion in osteocytes results in a fragile,
porous skeleton highly susceptible to fracture.  However, we have postulated
and shown that this pathway also plays a role in the osteocyte’s response to
either mechanical loading or to unloading.  In the absence of one allele of
b-Catenin in the osteocyte, anabolic response to mechanical loading is lost.
In response to unloading, b-Catenin has a different role according to
gender.  Female mice continue to lose bone with unloading whereas male mice
do not.  b-Catenin, its activators the Wnts, its inhibitors such as
sclerostin and DKK, and its receptors such as Lrp 4, 5, and 6 are all
players in the maintenance of bone.