93functions during the early stages of regeneration to repress VEGF induced re-
vascularization and to maintain the blastema in an avascular state. The data are
consistent with the conclusion that an avascular blastema is essential for promoting
the regenerative response.
9095
Normalized Volume (%
)BMP9
BSABMP9
PEDF100105110(^115) *
Fig. 5.5 ( a ) Transcripts for Pedf are found within the stump and the blastema ( arrowhead ) of the
regenerating 10 DPA digit. ( b and c ) μCT 3-D renderings at 14 DPI illustrate the inhibition of
regeneration in VEGF-treated digits. ( d and e ) Vegfa transcripts are absent in BSA treated control
digits, yet are detected ( arrowhead ) at 1 DPI in close association with the BMP9 soaked bead
( asterisk ). ( f and g ) By 7 DPI, Vegfa transcripts are detected in the proximal region of the BSA
treated digit, yet show an expanded expression domain ( arrowhead ) in BMP9 treated digits. ( h – j )
Application of PEDF in conjunction with BMP9 treatment rescues the BMP9-induced inhibition
of regeneration versus BMP9/BSA treated digits, resulting in a signifi cant increase in bone regen-
eration. ( k and l ) At 7 DPI, BMP9/BSA treated digits show attenuated Ocn expression, while
BMP9/PEDF-treated digits show an expanded domain of Ocn expression ( arrowheads ). ( m and n )
At 7 DPI, BMP9/BSA treated digits show an expanded domain of Vegfa expression, while BMP9/
PEDF treated digits show a paucity of Vegfa transcripts. Distal is to the right , dorsal is to the top.
Reprinted from Yu et al. [ 42 ]
5 Digit Regeneration in Mammals