The correlation of serum and synovial fluid (SF) pituitary adenylate cyclase-activating
polypeptide (PACAP) levels with disease progression of primary knee osteoarthritis
(OA) was explored. Radiographic severity of OA was determined by Kellgren-Lawrence
(K-L) grades. PACAP levels were measured by ELISA before treatment, and 4 and 8 wk
following hyaluronic acid (HA) injection. Levels of IL-1 and MMP-3 were also detected.
The numeric pain scale (NPS), revised Oxford Knee Score (OKS), and American Knee Society
Score (AKSS) were employed to evaluate to symptomatic severity. Receiver-operating-characteristic
(ROC) curve analysis was carried out to compare the diagnostic value of PACAP, IL-1,
and MMP-3 for the K-L grade. PACAP concentrations in SF but not serum were significantly
lower in OA patients compared with controls. SF PACAP levels were negatively associated
with K-L grades and higher NPS as well as worse AKSS and OKS. Further analysis demonstrated
that PACAP concentration in SF was negatively correlated with expressions of IL-1
as well as MMP-3 and may act as a marker for radiographic progression along with MMP-3.
Last, we found SF PACAP levels exhibited an incremental trend after HA injection.
These findings confirmed the crucial role of PACAP deficiency in the development of
primary knee OA.