J Rheum Dis.  2017 Feb;24(1):14-20. 10.4078/jrd.2017.24.1.14.

Interleukin-32 Gamma as a New Face in Inflammatory Bone Diseases

  • 1Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ejchang@amc.seoul.kr


Interleukin-32 (IL-32), a recently identified pro-inflammatory cytokine, is involved in the pathogenesis and progression of infections, cancer, chronic inflammation, and autoimmune disease. IL-32γ is the most active isoform in cell death and cell activation among nine distinct isoforms of IL-32. IL-32γ potentiates both osteogenic and osteoclastogenic capacities, and is critical in the coupling of bone resorption and bone formation for maintenance of bone homeostasis. IL-32γ is strongly associated with inflammatory bone disorders such as rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. In this review, we summarize current research on the role of IL-32γ in inflammatory bone disorders, highlighting this cytokine as a novel target for prognostic marker and control of these diseases.


IL-32γ; Osteogenesis; Rheumatoid arthritis; Ankylosing spondylitis; Osteoporosis

MeSH Terms

Arthritis, Rheumatoid
Autoimmune Diseases
Bone Diseases*
Bone Resorption
Cell Death
Protein Isoforms
Spondylitis, Ankylosing
Protein Isoforms


  • Figure 1. Molecular mechanisms of interleukin (IL)-32γ-me-diated bone metabolism. IL-32γ increases the level of Dik-koprf-1 (DKK-1)-targeting miR-29a, leading to osteoblast differentiation and subsequent increase in bone formation. Simultaneously, IL-32γ enhances receptor activator of nuclear factor-kappa B ligand (RANKL) production to activate osteoclast differentiation.

  • Figure 2. The effects of interleukin (IL)-32γ on bone remodeling in ankylosing spondylitis and osteoporosis. (A) Normal spine remodeling is balanced by the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. In the spinal joints of patients with ankylosing spondylitis, locally elevated IL-32γ suppresses Dikkoprf-1 (DKK-1), a Wnt inhibitor in the synovium, which enables differentiation of osteoblast and subsequent new abnormal bone formation; this effect overshadows the effect of IL-32γ on receptor activator of nuclear factor-kappa B ligand (RANKL)-mediated osteoclast differentiation. (B) Diminished level of systemic IL-32γ in osteoporosis patients results in elevated expression of DKK-1, which leads to low bone mass and high fracture risk; however, there are no significant differences in bone marrow IL-32γ level between osteoporotic hip fracture patients and no-fracture patients. TNF-α: tumor necrosis factor-α.

Cited by  1 articles

Role of IL-32 Gamma on Bone Metabolism in Autoimmune Arthritis
Oh Chan Kwon, Soohyun Kim, Seokchan Hong, Chang-Keun Lee, Bin Yoo, Eun-Ju Chang, Yong-Gil Kim
Immune Netw. 2018;18(3):.    doi: 10.4110/in.2018.18.e20.


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