Biology Reference
In-Depth Information
1
H
+
3
2
mineral
dissolution
cysteine proteinases
matrix metallopro-
teinases
degradation non-collagenous proteins
degradation of collagen
Fig. 8.9 Schematic presentation of the proposed sequence of activities of calvaria bone degrada-
tion as depicted from (Everts et al.
1998
).
Step 1
: lowering of the pH results in dissolution of the
mineral;
step 2
: cysteine proteinases digest non-collagenous proteins;
step 3
: matrix metallopro-
teinases digest the collagenous matrix. Between step 2 and 3 the pH increases to a level favourable
for MMPs to exert their activity
disturbed. Several studies demonstrated a close association between this integrin
and PA in the membrane. Which of the plasminogen activators is most important in
this process is not known yet, but Kubota et al. (Kubota et al.
2003
) showed a very
strong upregulation of uPA during osteoclast formation of RAW cells. This may
suggest that uPA is the more important of the two activators.
8.2.6.4 TRACP and Bone Degradation
TRACP is highly expressed by the osteoclast and used as a marker enzyme to
localize these cells in sections and cell cultures. Yet, its role in the digestion of bone
appears to be rather limited. Mice deficient for TRACP are characterized by a mild
osteopetrotic phenotype (Hayman et al.
1996
), indicating a slightly disturbed
resorption. Osteoclasts are present in normal numbers and they resorb bone. In a
subsequent study in which not only TRACP but also lysosomal acid phosphatase
was deleted, high levels of non-digested osteopontin were noted next to the
resorbing osteoclasts (Suter et al.
2001
). In line with other studies (Andersson
et al.
2003
) where TRACP was shown to dephosphorylate non-collagenous proteins
like osteopontin, it was concluded that TRACP is primarily involved in this process.
Next to dephosphorylation TRACP can also generate reactive oxygen species
(ROS) (Vaananen et al.
2000
). Data suggest that ROS may induce fragmentation of
matrix components ingested by the osteoclast (Halleen et al.
1999
,
2003
).
Not all osteoclasts express the same level of TRACP. Those harboring the
calvaria express much higher levels of this enzyme than osteoclasts in long bones
