Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct 18;294(42):15395-15407.
doi: 10.1074/jbc.RA119.010139. Epub 2019 Aug 28.

STAT3 Controls Osteoclast Differentiation and Bone Homeostasis by Regulating NFATc1 Transcription

Free PMC article

STAT3 Controls Osteoclast Differentiation and Bone Homeostasis by Regulating NFATc1 Transcription

Yiling Yang et al. J Biol Chem. .
Free PMC article


The transcription factor signal transducer and activator of transcription 3 (STAT3) plays a central role in cell survival and function. STAT3 has been demonstrated to participate in the maintenance of bone homeostasis in osteoblasts, but its role in osteoclasts in vivo remains poorly defined. Here, we generated a conditional knockout mouse model in which Stat3 was deleted in osteoclasts using a cathepsin K-Cre (Ctsk-Cre) driver. We observed that osteoclast-specific Stat3 deficiency caused increased bone mass in mice, which we attributed to impaired bone catabolism by osteoclasts. Stat3-deficient bone marrow macrophages (BMMs) showed decreased expression of nuclear factor of activated T cells, cytoplasm 1 (NFATc1), and reduced osteoclast differentiation determined by decreases in osteoclast number, tartrate-resistant acid phosphatase activity, and expression of osteoclast marker genes. Enforced expression of NFATc1 in Stat3-deficient BMMs rescued the impaired osteoclast differentiation. Mechanistically, we revealed that STAT3 could drive the transcription of NFATc1 by binding to its promoter. Furthermore, preventing STAT3 activation by using an inhibitor of upstream phosphorylases, AG490, also impaired osteoclast differentiation and formation in a similar way as gene deletion of Stat3 In summary, our data provide the first evidence that STAT3 is significant in osteoclast differentiation and bone homeostasis in vivo, and it may be identified as a potential pharmacological target for the treatment of bone metabolic diseases through regulation of osteoclast activity.

Keywords: NFAT transcription factor; STAT3; bone; osteoclast; osteoporosis; transgenic mice.

Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article

Similar articles

See all similar articles

Publication types

LinkOut - more resources