RT Journal
A1 Alman, Benjamin A.
T1 Multiple Hereditary Exostosis and Hedgehog Signaling: Implications for Novel Therapies
JF The Journal of Bone & Joint Surgery
JO The Journal of Bone & Joint Surgery
YR 2009
FD July 1
VO 91
IS Supplement_4
SP 63
OP 67
DO 10.2106/JBJS.I.00301
UL http://dx.doi.org/10.2106/JBJS.I.00301
AB 
Growth-plate chondrocytes go through a coordinated process of differentiation, resulting in the longitudinal growth of bones. The Indian hedgehog-parathyroid hormone-related protein (Ihh-PTHrP) pathway regulates the rate at which chondrocytes within the growth plate proliferate and differentiate, thus controlling the longitudinal growth of bones. Linkage studies and mutational analysis show that multiple hereditary exostosis is caused by mutations in the EXT genes, the products of which play a role in the diffusion of hedgehog proteins; a mutation in an EXT gene causes abnormal Ihh diffusion, leading to an osteochondroma. Hedgehog signaling remains activated in osteochondromas. Pharmacologic agents that inhibit hedgehog signaling are under development, and these agents may be useful in the treatment of osteochondromas or of chondrosarcomas that develop from malignant degeneration.