Bone Research · Published 2026-08-04 · DOI 10.1038/s41413-026-00546-0
Gaurav Swarnkar, Md Fahim Ahmad, Marwa Zeyad, Abdul Malik Tyagi, Musarrat Naaz, Gabriel Mbalaviele, Yousef Abu-Amer
Abstract Inflammation causes bone loss by dysregulating the differentiation and functions of osteoclasts, osteoblasts, and osteocytes. This process can be modeled by the expression of constitutively activated IKK2 (IKK2ca), a strategy that we leveraged to investigate the mechanisms through which inflammation negatively affects cells of the osteoblast/osteocyte lineage. We found that mice expressing IKK2ca in osteoblasts exhibit significant bone loss. Mechanistically, IKK2ca downregulates the expression of osteoblast genes while inducing the differentiation of bone-forming osteoblasts into catabolic osteocytes like cells, expressing high levels of Podoplanin, Fgf23, Dkk1 and Sclerostin. We term these atypical inflammatory osteocyte-like cells (aiOCy-L cells) as they highly express inflammatory and senescence markers and promote osteoclast differentiation as well. Additional data show that inflammation induces abnormal differentiation of OB into aiOCy-L cells through upregulating mTOR and glycolysis. In summary, we uncovered a mechanism by which inflammation alters osteoblast differentiation and fate decision via the IKK2/mTOR/glycolysis axis.
Abstract from DOAJ. Public domain (CC0 1.0).
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Swarnkar, G., Ahmad, M., Zeyad, M., et al. (2026). Inflammation driven by NF-ĸB compromises bone formation by inducing the differentiation of osteoblasts into atypical inflammatory osteocyte-like cells. Bone Research. https://doi.org/10.1038/s41413-026-00546-0