Abstract

Osteoimmunology investigations to-date have demonstrated the significant interactions between bone surface cells, osteoclasts and osteoblasts, and immune cells. However, there is a paucity of knowledge on osteocytes, cells embedded in the bone matrix, and their role in inflammation and inflammatory bone loss. Osteocytes communicate through various mechanisms; directly via dendritic processes and through secretion of proteins that can influence the formation and activity of osteoblasts and osteoclasts. Some osteocyte proteins (e.g., interleukin-6 and RANKL) also have roles within the immune system. In the context of mechanical loading/unloading, the regulatory role of osteocytes is well understood. More recent data on osteocytes in various inflammatory models suggest they may also aid in orchestrating inflammation-induced changes in bone turnover. In inflammatory conditions, osteocytes express multiple pro-inflammatory cytokines which are associated with increases in bone resorption and declines in bone formation. Cytokines are known to also influence cell population growth, maturation, and responsiveness via various signaling modalities, but how they influence osteocytes has not been greatly explored. Furthermore, osteocytes may play regulatory roles in orchestrating bone's response to immunological changes in inflammatory conditions. This review will address what is known about osteocyte biology in physiological conditions and in response to varying immunological conditions, as well as highlight key areas of interest for future investigations.

Highlights

  • Bone loss is an imbalance of bone formation and resorption which occurs in many conditions including disuse, aging, and chronic inflammatory conditions such as inflammatory bowel disease [1], rheumatoid arthritis [2], psoriasis [3], and systemic lupus erythematosus [4]

  • In addition to osteoblasts and osteoclasts, other cell types residing in the bone environment such as bone marrow stromal cells and osteoblast/osteoclast-precursor cells can be influenced in their function by cytokines [32, 33]

  • We previously demonstrated in rats with inflammatory bowel disease decreased osteocyte density and increased apoptosis concurrent with elevated osteocyte tumor necorosis factor (TNF)-α [68, 69]

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Summary

The Role of Osteocytes in Inflammatory Bone Loss

The Role of Osteocytes in Inflammatory Bone Loss. Osteocytes express multiple pro-inflammatory cytokines which are associated with increases in bone resorption and declines in bone formation. Osteocytes may play regulatory roles in orchestrating bone’s response to immunological changes in inflammatory conditions. Multiple other conditions with known inflammatory components are associated with bone loss and increased bone fragility including type 2 diabetes [9], chronic kidney disease [10], spinal cord injury [11], and aging-related osteoporosis [12]. While the role of immune factors and inflammation on various bone cells (osteoblasts, osteoclasts, stromal cells, marrow immune cells, bone precursor cells) have been extensively researched [13], the osteocyte response to inflammatory stimuli has been comparably less investigated. Osteocytes have increasingly become appreciated as key regulators of both osteoclasts and osteoblasts, orchestrating changes in bone turnover

AND BONE
OSTEOCYTE BIOLOGY
ADAPTATIONS TO MECHANICAL STRAINS
OSTEOCYTES AND CYTOKINES
INFLAMMATORY SIGNALS
CONCLUSIONS
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