Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27742498
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Bone
2017 ; 96
(ä): 29-37
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Role and mechanism of action of sclerostin in bone
#MMPMID27742498
Delgado-Calle J
; Sato AY
; Bellido T
Bone
2017[Mar]; 96
(ä): 29-37
PMID27742498
show ga
After discovering that lack of Sost/sclerostin expression is the cause of the
high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive
animal experimentation and clinical studies demonstrated that sclerostin plays a
critical role in bone homeostasis and that its deficiency or pharmacological
neutralization increases bone formation. Dysregulation of sclerostin expression
also underlies the pathophysiology of skeletal disorders characterized by loss of
bone mass, as well as the damaging effects of some cancers in bone. Thus,
sclerostin has quickly become a promising molecular target for the treatment of
osteoporosis and other skeletal diseases, and beneficial skeletal outcomes are
observed in animal studies and clinical trials using neutralizing antibodies
against sclerostin. However, the anabolic effect of blocking sclerostin decreases
with time, bone mass accrual is also accompanied by anti-catabolic effects, and
there is bone loss over time after therapy discontinuation. Further, the cellular
source of sclerostin in the bone/bone marrow microenvironment under physiological
and pathological conditions, the pathways that regulate sclerostin expression and
the mechanisms by which sclerostin modulates the activity of osteocytes,
osteoblasts, and osteoclasts remain unclear. In this review, we highlight the
current knowledge on the regulation of Sost/sclerotin expression and its
mechanism(s) of action, discuss novel observations regarding its role in
signaling pathways activated by hormones and mechanical stimuli in bone, and
propose future research needed to understand the full potential of therapeutic
interventions that modulate Sost/sclerostin expression.
free
free
free
