We previously reported increased release of the
excitatory amino acid (EAA)
neurotransmitters,
glutamate and
aspartate, during the early stage of experimental
osteoarthritis (OA). Our present objective was to study the effect of
intraarticular injection of
hyaluronic acid (HA) on OA development, and to analyze concomitant changes in EAA levels in
dialysates of anterior cruciate ligament-transected (ACLT) knee joints. OA was induced in Wistar rats by ACLT of one hindlimb; the knee of the other hindlimb was used as the
sham-operated control. HA group (n = 12) were injected intraarticularly in the ACLT knee with 1 mg of HA once a week for 5 consecutive weeks, starting at 8 weeks after surgery. Saline group (n = 12) were injected as above with
normal saline. The
sham-operated group, underwent arthrotomy, but not ACLT, and received no treatment (n = 14). Twenty weeks after surgery, knee joint
dialysates were collected by microdialysis and EAA levels assayed by high-performance liquid chromatography, and gross morphological examination and histopathological evaluation were performed on the medial femoral condyles and synovia. Rats receiving intraarticular HA
injections showed a significantly lower degree of cartilage degeneration on the medial femoral condyle at both the macroscopic level and on the Mankin grading scale than rats receiving saline
injections. Intraarticular HA treatment also suppressed
synovitis. Moreover,
glutamate and
aspartate levels were significantly reduced in the HA group compared to the saline group.
Intraarticular injection of HA limits articular cartilage and synovium damage and OA formation, and, in parallel, reduces EAA levels in ACLT joint
dialysates. This study suggests that the underlying mechanism of the anti-inflammatory effect of HA is to inhibit
glutamate and
aspartate release in ACLT knee joints, which attenuates the early development of OA.