In vivo protective effect of adipsin-deficiency on spontaneous knee osteoarthritis in aging mice

Abstract

The adipokine adipsin is an emerging mediator of human osteoarthritis (OA) progression. Here, we investigated its in vivo role in the development of spontaneous OA in aging mice. We compared articular knee joint morphology, histology in knee cartilage, synovial membrane, subchondral bone, meniscus, and anterior cruciate ligament (ACL), and chondrogenesis in the ACL from adipsin-deficient (Df-/-) and wild-type (Df +/+) in 20-week-and 20-month-old mice. Serum levels of a panel of adipokines, inflammatory factors, and metalloproteases known to be implicated in OA were investigated. Data first reveal that the early manifestation of OA appeared in the ACL of 20-week-old mice, progressing to severe alterations in the 20 month-old wild-type mice. Further results demonstrated that adipsin-deficiency protected the articular tissues from spontaneous OA progression and triggered significantly higher serum levels of the adipokines adiponectin and FGF-21 while lowering levels of the inflammatory factor interleukin 6 (IL-6) in both young and old mice. This work further underlines the clinical relevance of adipsin as a novel therapeutic approach of human OA. Moreover, this study shows the potential beneficial effect of the adipokine FGF-21 against OA, and provides support for this factor to be a new biomarker and/or target of primary OA therapeutic avenues.

Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway

“…In addition, Li et al observed OA patients had significantly higher serum and synovial fluid FGF21 concentration compared to that in the controls [34]. Paré et al found a potential beneficial effect of FGF-21 against OA [35]. Given the potential therapeutic effect of FGF21, we hypothesized that FGF21 might reduce the progression of osteoarthritis, which was verified in the present study.…”

Adipose tissue is a critical regulator of osteoarthritis

“…It is important to note that LD mice also lack other signaling molecules, such as adipsin, or complement factor D, which cleaves factor B to initiate alternative complement-pathway activity (12). Previous studies have demonstrated a protective effect of adipsin deficiency on both spontaneous and posttraumatic OA pathogenesis (15,40), so it is unclear whether adipsin deficiency protects against joint damage in the present studies. Our ongoing work is interrogating the role of adipsin-knockout animals in the presence of HFD and OA to determine if the absence of adipsin signaling in particular protects against cartilage damage in the LD mouse.…”

Adipose Tissue is a Critical Regulator of Osteoarthritis

“…LD mice have an absence of adipsin, or complement factor D, which cleaves factor B to initiate alternative complement pathway activity (12). Previous studies have demonstrated a protective effect of adipsin deficiency on both spontaneous and post-traumatic OA pathogenesis (13,37), so it is unclear if adipsin deficiency is the protective adipokine mechanism modulating joint damage in the present studies. Our ongoing work is interrogating the role of adipsin knockout animals in the presence of high fat diet and osteoarthritis to determine if the absence of adipsin signaling in particular protects against cartilage damage in the LD mouse.…”