Osteoimmunology

Abstract

Osteoimmunology is an interdisciplinary research field combining the exciting fields of osteology and immunology. An observation that contributed enormously to the emergence of osteoimmunology was the accelerated bone loss caused by inflammatory diseases such as rheumatoid arthritis. Receptor activator of nuclear factor ĸB ligand (RANKL), which is the main regulator of osteoclastogenesis, was found to be the primary culprit responsible for the enhanced activation of osteoclasts: activated T cells directly and indirectly increased the expression of RANKL, and thereby promoted osteoclastic activity. Excessive bone loss is not only present in inflammatory diseases but also in autoimmune diseases and cancer. Furthermore, there is accumulating evidence that the very prevalent skeletal disorder osteoporosis is associated with alterations in the immune system. Meanwhile, numerous connections have been discovered in osteoimmunology beyond merely the actions of RANKL. These include the importance of osteoblasts in the maintenance of the hematopoietic stem cell niche and in lymphocyte development as well as the functions of immune cells participating in osteoblast and osteoclast development. Furthermore, research is being done investigating cytokines, chemokines, transcription factors and co-stimulatory molecules which are shared by both systems. Research in osteoimmunology promises the discovery of new strategies and the development of innovative therapeutics to cure or alleviate bone loss in inflammatory and autoimmune diseases as well as in osteoporosis. This review gives an introduction to bone remodeling and the cells governing that process and summarizes the most recent discoveries in the interdisciplinary field of osteoimmunology. Furthermore, an alternative large animal model will be discussed and the pathophysiological alterations of the immune system in osteoporosis will be highlighted.

Bovine lactoferrin improves bone mass and microstructure in ovariectomized rats via OPG/RANKL/RANK pathway

“…OPG is an endogenous antagonist of RANKL and inhibits RANKL action by acting as a soluble decoy receptor, thus balancing bone turnover [28] . In bone, RANKL is expressed most abundantly in MSCs, osteoblasts and T cells [29] . Despite OPG being a known inhibitor of RANKL, its biological effect may depend on the molar ratio between RANKL and OPG [30] .…”

Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome

“…However, there was no cortical bone loss in these animals. When the normal interaction between the immune and skeletal systems is disrupted by chronic inflammation the balance favors net bone loss (Rauner et al 2006). TNFα, IL-1β and IL-6 regulate bone resorption by stimulating expression of receptor activator of NF-κB ligand (RANKL) in osteoblasts (Thomson et al 1986;Thomson et al 1987;Kishimoto 1989;Rauner et al 2006), which is necessary for osteoclast differentiation (Yasuda et al 1998).…”

N-acetyl Cysteine Alleviates Cytotoxicity of Bone Substitute

“…Detoxified Bone Substitute by NAC 415 (Rauner et al, 2007). It will be of great interest for further research to examine the influences of bone substitute and the effect of NAC on the osteoimmunological network.…”