sLZIP functions as a key modulator of bone remodeling by regulating the crosstalk between osteoblasts and osteoclasts

Park, Sungyeon; Kim, Jeonghan; Ko, Jesang

doi:10.1038/s12276-025-01414-3

상세 보기

sLZIP functions as a key modulator of bone remodeling by regulating the crosstalk between osteoblasts and osteoclasts

Park, Sungyeon;
Kim, Jeonghan;
Ko, Jesang

Citations

WEB OF SCIENCE

5

Citations

SCOPUS

4

초록

Human small leucine zipper protein (sLZIP) regulates the differentiation of both osteoblasts (OBs) and osteoclasts (OCs). However, the regulatory role of sLZIP in bone remodeling and its involvement in bone disorders remain unclear. Here we investigated the role of sLZIP in bone remodeling and its importance in the development of cell therapies for bone diseases. sLZIP increased bone mass in an osteoporosis mouse model. Moreover, bone mass was lower in mesenchymal stem cell-specific murine LZIP-1/2 knockout (Osx-LZIP-1/2fl/fl) mice than in control LZIP-1/2fl/fl mice. Compared with control mice, Osx-LZIP-1/2fl/fl mice presented delayed bone fracture healing in osteoporosis. Conditioned medium from OBs differentiated from adipose-derived stem cells from Osx-LZIP-1/2fl/fl mice attenuated OC formation and the migration of bone marrow-derived macrophages. However, conditioned medium from OCs from sLZIP transgenic mice induced OB differentiation and migration. sLZIP regulates the secretion of OC-derived sphingosine-1-phosphate, which induces OB differentiation. sLZIP also regulates OB-derived WNT16, which inhibits OC differentiation. Therefore, sLZIP is a key modulator of the crosstalk between OBs and OCs and promotes bone remodeling and fracture healing in osteoporosis. In addition, sLZIP-overexpressing adipose-derived stem cells promote bone formation and repair in osteoporosis. sLZIP is an excellent target for stem cell-based treatment of osteoporosis.

키워드

Colony Stimulating Factor 1; Ibuprofen; Parathyroid Hormone; Ez Cytox; Ctan V1.14 Analysis Software; Ctvox V2.6 Three- Dimensional Visualization Software; Data Viewer V1.5 Reconstruction Software; Dulbecco’s Modified Eagle Medium; Evagreen-express Master Mix; Graphpad Prism 5; Lightcycler 480 Ii; Minibest Universal Rna Extraction Kit; Mouse S1p Enzyme Linked Immunosorbent Assay Kit; Nrecon V1.6 Reconstruction Software; Skyscan1172 Micro-computed Tomography Scanning; Somnosuite Low-flow Anesthesia System; Spectramax I3x Spectrophotometer; T100 Thermal Cycler; Tracp/alp Double-staining Kit; Collagen Type 1; Colony Stimulating Factor 1; Ez Cytox; Ibuprofen; Immunomodulating Agent; Parathyroid Hormone; Sphingosine Kinase 1; Transcription Factor Runx2; Tumor Necrosis Factor; Adipogenesis; Adipose Derived Stem Cell; Animal Cell; Animal Experiment; Animal Model; Animal Tissue; Apoptosis; Article; Bone Development; Bone Metabolism; Bone Regeneration; Bone Remodeling; Callus; Cell Culture; Cell Migration; Cell Proliferation; Coculture; Controlled Study; Enzyme Linked Immunosorbent Assay; Flow Cytometry; Fracture Healing; Gene Expression; Histology; Homeostasis; Human; Human Cell; Immunofluorescence; In Vitro Study; Mesenchymal Stem Cell; Micro-computed Tomography; Mouse; Nonhuman; Ossification; Osteoblast; Osteoclast; Osteolysis; Osteoporosis; Protein Expression; Real Time Polymerase Chain Reaction; Rna Isolation; Western Blotting; Animal; Cell Communication; Cell Differentiation; Cytology; Disease Model; Genetics; Knockout Mouse; Metabolism; Pathology; Transgenic Mouse; Animals; Bone Remodeling; Cell Communication; Cell Differentiation; Disease Models, Animal; Fracture Healing; Humans; Mesenchymal Stem Cells; Mice; Mice, Knockout; Mice, Transgenic; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; MESENCHYMAL STEM-CELLS; OSTEOPOROSIS; BISPHOSPHONATES; INVOLVEMENT; EXPRESSION; MIGRATION

제목: sLZIP functions as a key modulator of bone remodeling by regulating the crosstalk between osteoblasts and osteoclasts

저자: Park, Sungyeon; Kim, Jeonghan; Ko, Jesang

DOI: 10.1038/s12276-025-01414-3

발행일: 2025-03

유형: Article

저널명: Experimental & Molecular Medicine

권: 57

호: 3

페이지: 601 ~ 615