Osteocyte-related cytokines regulate osteoclast formation and bone resorption

Hideki Kitaura, Aseel Marahleh, Fumitoshi Ohori, Takahiro Noguchi, Wei Ren Shen, Jiawei Qi, Yasuhiko Nara, Adya Pramusita, Ria Kinjo, Itaru Mizoguchi

Research output: Contribution to journalReview articlepeer-review

133 Citations (Scopus)


The process of bone remodeling is the result of the regulated balance between bone cell populations, namely bone-forming osteoblasts, bone-resorbing osteoclasts, and the osteocyte, the mechanosensory cell type. Osteoclasts derived from the hematopoietic stem cell lineage are the principal cells involved in bone resorption. In osteolytic diseases such as rheumatoid arthritis, periodontitis, and osteoporosis, the balance is lost and changes in favor of bone resorption. Therefore, it is vital to elucidate the mechanisms of osteoclast formation and bone resorption. It has been reported that osteocytes express Receptor activator of nuclear factor κΒ ligand (RANKL), an essential factor for osteoclast formation. RANKL secreted by osteocytes is the most important factor for physiologically supported osteoclast formation in the developing skeleton and in pathological bone resorption such as experimental periodontal bone loss. TNF-α directly enhances RANKL expression in osteocytes and promotes osteoclast formation. Moreover, TNF-α enhances sclerostin expression in osteocytes, which also increases osteoclast formation. These findings suggest that osteocyte-related cytokines act directly to enhance osteoclast formation and bone resorption. In this review, we outline the most recent knowledge concerning bone resorption-related cytokines and discuss the osteocyte as the master regulator of bone resorption and effector in osteoclast formation.

Original languageEnglish
Article number5169
JournalInternational Journal of Molecular Sciences
Issue number14
Publication statusPublished - 2020
Externally publishedYes


  • Bone
  • Cytokine
  • Osteoclast
  • Osteocyte


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