The Journal of Bone and Joint Surgery, Vol 74, Issue 9 1375-1384, Copyright © 1992 by Journal of Bone and Joint Surgery, Inc
Changes in growth-plate morphology associated with rejection of rat-limb allografts
M Mohtai, T Hotokebuchi, K Arai and Y Sugioka
Department of Orthopaedic Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Histological and electron microscopic studies were performed to demonstrate
the changes in the morphology of the growth plate that occur in allografts
obtained from the limbs of growing rats. A genetically defined model was
used in which the right hindlimbs of Lewis rats were orthotopically
transplanted into Fischer-344 recipient rats. These strains are matched for
major histocompatibility antigens but mismatched for minor
histocompatibility antigens. The disparity at the minor histocompatibility
complex between the Lewis donors and the Fischer recipients creates a weak
histocompatibility barrier to transplantation. Lewis-to-Lewis syngeneic
limb grafts were used as controls. The proximal parts of the transplanted
tibiae were excised during acute rejection of the allograft on days 1, 5,
8, 11, 14, and 28 postoperatively. During rejection, a widened zone of
calcified cartilage in the growth plate was observed at eleven days; this
zone increased progressively thereafter. The number of chondroclasts in the
primary spongiosa of the metaphysis had decreased significantly at eleven
days, and chondroclasts had disappeared completely at fourteen days, in
association with mononuclear cell infiltration. Electron microscopic
examination revealed inactive morphology in some chondroclasts at eight
days, and the number of inactive chondroclasts had increased significantly
on day 11. At fourteen days, there were no viable chondroclasts in the
primary spongiosa, and only remnants of degenerated chondroclasts were
present. These findings suggest that the chondroclasts were early targets
of rejection and their loss resulted in the cessation of resorption of the
calcified cartilage. However, the proliferation and maturation of
chondrocytes in the growth plate and the calcification of the matrix
continued, despite progression of rejection in the metaphysis. Thus,
survival of the chondrocytes and rejection of the chondroclasts apparently
led to the formation of a widened calcifying zone in the growth plate.