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Review
. 2020 Dec 11;18(1):479.
doi: 10.1186/s12967-020-02664-7.

The roles of osteocytes in alveolar bone destruction in periodontitis

Xiaofei Huang  1   2 , Mengru Xie  1   2 , Yanling Xie  1   2 , Feng Mei  1   2 , Xiaofeng Lu  1   2 , Xiaoshuang Li  3   4 , Lili Chen  5   6
Affiliations
Review

The roles of osteocytes in alveolar bone destruction in periodontitis

Xiaofei Huang et al. J Transl Med. .

Abstract

Periodontitis, a bacterium-induced inflammatory disease that is characterized by alveolar bone loss, is highly prevalent worldwide. Elucidating the underlying mechanisms of alveolar bone loss in periodontitis is crucial for understanding its pathogenesis. Classically, bone cells, such as osteoclasts, osteoblasts and bone marrow stromal cells, are thought to dominate the development of bone destruction in periodontitis. Recently, osteocytes, the cells embedded in the mineral matrix, have gained attention. This review demonstrates the key contributing role of osteocytes in periodontitis, especially in alveolar bone loss. Osteocytes not only initiate physiological bone remodeling but also assist in inflammation-related changes in bone remodeling. The latest evidence suggests that osteocytes are involved in regulating bone anabolism and catabolism in the progression of periodontitis. The altered secretion of receptor activator of NF-κB ligand (RANKL), sclerostin and Dickkopf-related protein 1 (DKK1) by osteocytes affects the balance of bone resorption and formation and promotes bone loss. In addition, the accumulation of prematurely senescent and apoptotic osteocytes observed in alveolar bone may exacerbate local destruction. Based on their communication with the bloodstream, it is noteworthy that osteocytes may participate in the interaction between local periodontitis lesions and systemic diseases. Overall, further investigations of osteocytes may provide vital insights that improve our understanding of the pathophysiology of periodontitis.

Keywords: Apoptosis; Osteocyte; Periodontitis; RANKL; Sclerostin; Senescence.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Osteocytes initiate bone remodeling through the regulation of osteoclasts and osteoblasts. (Top) Osteocytes express RANKL to promote, and OPG to inhibit, osteoclast generation and bone resorption. (Bottom) Osteocytes also secrete sclerostin and DKK1 to inhibit osteoblast formation and activity
Fig. 2
Fig. 2
RANKL expression in osteocytes is upregulated under LPS and TNF-α stimulation. LPS binds to TLRs and activates the MAPK/ERK1/2 pathway, which promotes IL-6 production in osteocytes. IL-6 subsequently enhances RANKL expression by facilitating STAT signal transduction. TNF-α can promote RANKL generation through the NF-κB pathway and the ERK1/2, JNK and P38 MAPK pathways
Fig. 3
Fig. 3
TNF-α mediates sclerostin expression in osteocytes via the NF-κB pathway
Fig. 4
Fig. 4
Premature osteocyte senescence and its downstream effects in periodontitis. In periodontitis, stimulation by bacteria (a) and inflammatory cells (b) drives osteocytes to undergo premature senescence (1). Senescent osteocytes (c) express SASP (2), which reinforces osteoclast (d)-mediated bone resorption but inhibits osteoblast (e)-mediated bone formation. Senescent osteocytes can induce senescence in adjacent cells through SASP (3) and/or cell–cell contact (4)
Fig. 5
Fig. 5
Apoptosis of osteocytes directly or indirectly promotes osteoclastogenesis and related bone resorption. Apoptotic osteocytes can release, or induce surrounding osteocytes to express, RANKL to modulate preosteoclast adherence and differentiation into osteoclasts. Secondary osteocyte necrosis can induce local inflammation and promote osteoclast formation and activation
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