Lhx2 regulates bone remodeling in mice by modulating RANKL signaling in osteoclasts
Open accessAbstract
The LIM homeobox 2 (Lhx2) transcription factor Lhx2 has a variety of functions, including neural induction, morphogenesis, and hematopoiesis. Here we show the involvement of Lhx2 in osteoclast differentiation. Lhx2 was strongly expressed in osteoclast precursor cells but its expression was significantly reduced during receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis. Overexpression of Lhx2 in bone marrow-derived monocyte/macrophage lineage cells (BMMs), which are osteoclast precursor cells, attenuated RANKL-induced osteoclast differentiation by inhibiting the induction of nuclear factor of activated T cells c1 (NFATc1). Interestingly, interaction of Lhx2 proteins with c-Fos attenuated the DNA-binding ability of c-Fos and thereby inhibited the transactivation of NFATc1. Furthermore, Lhx2 conditional knockout mice exhibited an osteoporotic bone phenotype, which was related with increased osteoclast formation in vivo. Taken together, our results suggest that Lhx2 acts as a negative regulator of osteoclast formation in vitro and in vivo. The anti-osteoclastogenic effect of Lhx2 may be useful for developing a therapeutic strategy for bone disease.
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A few studies have revealed that homeobox genes, such as Lhx2, Dlx5, and Pax6, affect osteoclast formation.
“A few studies have revealed that homeobox genes, such as Lhx2, Dlx5, and Pax6, affect osteoclast formation44–46”
From Targeting Msx2 as a brake in the fusion fate of osteoclasts and an anabolic therapy in pre-clinical models of osteoporosis (2025) · cites this paper as [44]
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References 34 · Cited by 26
- Authors
- Kim, J. H., Youn, B. U., Kim, K., Moon, J. B., Lee, J., Nam, K.-I. I., Park, Y.-W., O'Leary, D. D. M., Kim, K. K., & Kim, N.
- Affiliations
- Chonnam National University (KR)
- Corresponding author
- Kim, N
- ORCID
- Moon, J B
- Venue
- Cell Death & Differentiation
- Published
- 2014-06-06
- Volume
- 21
- Issue
- 10
- Pages
- 1613-1621
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- PMC
- PMC4158686
- OpenAlex
- W2161696867
- Cited by
- 26
- References
- 34
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 1 · 2014: 1
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- Ministry of Science, ICT and Future Planning (2011‐0030132)
- National Research Foundation of Korea (2011‐0030132)
- Medical Research Council (2011-0030132)
- National Eye Institute (R01EY007025)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- Lhx2, LIM homeobox transcription factor, osteoclastogenesis, RANKL signaling, bone remodeling, NFATc1, c-fos, osteoporosis, bone marrow-derived macrophages, transcriptional regulation, bone disease therapy
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Gene Expression Regulation, Macrophages, Osteoclasts, Osteogenesis, Osteoporosis, Transcription Factors, Signal Transduction, Down-Regulation, Bone Remodeling, Proto-Oncogene Proteins c-fos, Mice, Knockout, RNA Interference, RNA, Small Interfering, NFATC Transcription Factors, Mice, RANK Ligand, LIM-Homeodomain Proteins
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