Title:The Dramatic Role of IFN Family in Aberrant Inflammatory Osteolysis
Volume: 21
Issue: 2
关键词:
干扰素(IFNs)、成骨细胞-成骨细胞串扰、骨稳态、炎症性骨破坏疾病、骨骼、骨形成的成骨细胞。
摘要: Skeletal system has been considered a highly dynamic system, in which bone-forming
osteoblasts and bone-resorbing osteoclasts go through a continuous remodeling cycle to maintain
homeostasis of bone matrix. It has been well acknowledged that interferons (IFNs), acting as a subgroup
of cytokines, not only have crucial effects on regulating immunology but also could modulate
the dynamic balance of bone matrix. In the light of different isoforms, IFNs have been divided
into three major categories in terms of amino acid sequences, recognition of specific receptors and
biological activities. Currently, type I IFNs consist of a multi-gene family with several subtypes, of
which IFN-α exerts pro-osteoblastogenic effects to activate osteoblast differentiation and inhibits
osteoclast fusion to maintain bone matrix integrity. Meanwhile, IFN-β suppresses osteoblast-mediated
bone remodeling as well as exhibits inhibitory effects on osteoclast differentiation to attenuate
bone resorption. Type II IFN constitutes the only type, IFN-γ, which exerts regulatory effects on osteoclastic
bone resorption and osteoblastic bone formation by biphasic ways. Interestingly, type III
IFNs are regarded as new members of IFN family composed of four members, including IFN-λ1
(IL-29), IFN-λ2 (IL-28A), IFN-λ3 (IL-28B) and IFN-λ4, which have been certified to participate in
bone destruction. However, the direct regulatory mechanisms underlying how type III IFNs modulate
the metabolic balance of bone matrix, remains poorly elucidated. In this review, we have summarized
functions of IFN family during physiological and pathological conditions and described
the mechanisms by which IFNs maintain bone matrix homeostasis via affecting the osteoclast-osteoblast
crosstalk. In addition, the potential therapeutic effects of IFNs on inflammatory bone destruction
diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and infectious bone diseases
are also well displayed, which are based on the predominant role of IFNs in modulating the dynamic
equilibrium of bone matrix.
