Mechanical stress plays an important role in tissue morphogenesis and extracellular
matrix metabolism. However, little is known about the effects of reduced loading without
restriction of joint motion on the patella. We investigated the effects of long-term
skeletal unloading on patellar cartilage and subchondral bone and systemic collagen
II metabolism. Nine-week-old male F344/N rats (n=128) were randomly divided into two
groups: caged control (C) and tail suspended (TS). Hindlimbs of the TS rats were subjected
to unloading for up to 12 weeks. Sequential changes in the patellar cartilage and
subchondral bone were analyzed macroscopically, by pathological findings and histomorphologically.
All animals received double tidemark fluorochrome labeling prior to sacrifice. Glycosaminoglycan
(GAG) content in patellar cartilage, cross-linked C-telopeptide of type II collagen
(CTx-II) in 24-h urine and type II procollagen-C-peptide (pCol-II-C) in sera were
also measured by DMB assay, ELISA and EIA, respectively. In the TS group, GAG content
was significantly reduced only during the first 3 weeks. No further significant decrease
was found. Alkaline phosphatase (ALP) activity was increased, especially at the deep
zone. Tidemark mineral apposition rate (MAR) was temporally increased, which resulted
in an increase in the ratio of calcified cartilage to the entire cartilage. In the
medial part, in addition, thickness of the entire cartilage was decreased by temporal
acceleration of subchondral ossification advancement and, in the medial margin, a
full-thickness cartilage defect was revealed in 88.6% of TS rats. However, the remaining
articular surface was free from fibrillation. While urinary CTx-II was significantly
increased during the experimental periods, serum pCol-II-C was significantly decreased
at the early phase. There were significant correlations between the urinary CTx-II
levels and tidemark MAR. Our results provided evidence that skeletal unloading increased
ALP activity at the deep zone and temporally accelerated tidemark advancement associated
with a decrease in proteoglycan content. In addition, skeletal unloading temporally
accelerated subchondral ossification advancement in the medial part of the patella
and finally induced a full-thickness patellar cartilage defect without any fibrillation
at the remaining articular surface by additional subchondral bone modeling and possible
retarded cartilage growth, which was through a different mechanism than overloading.