- 作者: Janja Zupan, Radko Komadina and Janja Marc
- 作者服務機構: University of Ljubljana, Faculty of Pharmacy, Department of Clinical Biochemistry, Ljubljana, Slovenia
- 中文摘要: --
- 英文摘要:
Background: Pro-inflammatory cytokines possess osteoclastogenic or anti-osteoclastogenic activities. They
influence osteoclasts directly or via the receptor activator of nuclear factor κB (RANK),
RANK ligand (RANKL) and osteoprotegerin (OPG) system. Recent evidence suggests that
inflammation may play a role in osteoporosis (OP) and osteoarthritis (OA). We aimed
therefore to determine whether there is a difference between both groups: first, in the
expression of the osteoclastogenic and anti-osteoclastogenic cytokines, second, in correlation
of these cytokines with bone mineral density (BMD) and levels of bone turnover markers
(BTM) and third, in correlation between the expression of these cytokines and osteoclast
specific genes and RANK/RANKL/OPG genes.
Methods: Human bone samples from 54 age and sex matched patients with OP or OA were collected
during hip arthroplasty surgery. The expression of 25 genes encoding pro-inflammatory
cytokines, their receptors, osteoclast specific genes and RANK/RANKL/OPG genes was
measured using quantitative real-time PCR. Total hip, femoral neck and lumbar spine BMD
and BTM in blood samples were measured. The comparison between OP and OA was
assessed using Student’s t-test or Mann–Whitney U test and correlations between gene
expression, BMD and BTM were determined using nonparametric correlation.
Results: The results demonstrated a higher expression of interleukin (IL)-6 and IL-1α in OP, and
interferon (IFN)-γ in OA (p < 0.0005). Negative correlations of total hip BMD with tumor
necrosis factor-α (TNF-α) in OA and with RANKL/RANK in OP were found (p < 0.05).
Significant correlations with BTM were shown for IL-1α and IFN-γ in OP (rho = 0.608 and
−0.634) and for TNF-α, IL-6 and transforming growth factor-β1 (TGF-β1) in OA (rho =
0.591, -0.521 and 0.636). Results showed OP specific negative correlations (IFN-γ with
ITGB3, IFN-β1with CTSK, tartrate resistant acid phosphatase (TRAP), CALCR, RANK,
RANKL, IL-1α with CTSK, OPG, IL-17A with CALCR) and positive (TGF-β1 with CTSK,
TRAP, RANK), and OA specific negative (IL-1α with osteoclast associated immunoglobulinlike
receptor (OSCAR), TNF-α with RANK, RANKL, OPG) and positive (IL-6 with RANK,
RANKL, OPG) correlations.
Conclusions: Our results demonstrate that the relationship between osteoclastogenic and antiosteoclastogenic
pro-inflammatory cytokines differs in human OP and OA bone and could
present an important factor for characteristics of OP and OA bone phenotypes. - 中文關鍵字: --
- 英文關鍵字: Interleukins, Interferons, TNF-α, TGF-β1, β3 integrin, Cathepsin K, OSCAR