Hyaluronic acid attenuates osteoarthritis development in the anterior cruciate ligament-transected knee: Association with excitatory amino acid release in the joint dialysate.
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.
Graduate Institute of Medical Science, National Defense Medical Center, #325, Chenggung Road, Section 2, Neihu 114, Taipei, Taiwan, Republic of China.
Yen-Hsuan
YH
Jean
Zhi-Hong
ZH
Wen
Yi-Chen
YC
Chang
Herng-Sheng
HS
Lee
Shih-Peng
SP
Hsieh
Ching-Tang
CT
Wu
Chun-Chang
CC
Yeh
Chih-Shung
CS
Wong
D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D001224:Aspartic Acid / Q000378:metabolism; D002358:Cartilage, Articular / Q000473:pathology; D018846:Excitatory Amino Acids / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D007718:Knee Injuries / Q000150:complications* / Q000473:pathology; D008297:Male; D017551:Microdialysis; D010003:Osteoarthritis / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D018846:Excitatory Amino Acids; D001224:Aspartic Acid; D018698:Glutamic Acid; D006820:Hyaluronic Acid