TY - JOUR
T1 - The role of small leucine zipper protein in osteoclastogenesis and its involvement in bone remodeling
AU - Kim, Seukun
AU - Park, Sungyeon
AU - Kang, Minsoo
AU - Ko, Jesang
N1 - Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning ( NRF-2017R1E1A1A01073955 ) and the Korea University Grant.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/11
Y1 - 2020/11
N2 - Bone remodeling is critical to maintain the quality of bone tissues and to heal bone tissue injury. Osteoclasts and osteoblasts are special types of cells involved in this event. In particular, the resorption activity of mature osteoclasts is required for the formation of new bones. Human small leucine zipper protein (sLZIP) is known to induce the osteoblast differentiation of mesenchymal stem cells. However, the roles of sLZIP in osteoclast differentiation and bone remodeling have not been explored. In this study, we investigated the roles of sLZIP in regulating osteoclast formation and in the bone remodeling process using sLZIP transgenic (TG) mice. Tibiae from sLZIP TG mice contained more osteoclasts than those from wild type (WT) mice. Bone marrow-derived macrophages (BMM) from sLZIP TG mice showed increased differentiation into osteoclasts compared with BMM from WT mice. sLZIP bound to the promotor and induced the expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and its target osteoclastogenic genes. To understand the role of sLZIP in bone remodeling, a bone-defect model was generated. Results of micro-CT scanning and histologic analysis demonstrated that sLZIP TG mice have faster bone formation during healing compared with WT mice. Notably, the soft callus around the defect area was replaced faster by hard callus in sLZIP TG mice than in WT mice. These findings suggest that sLZIP promotes osteoclast differentiation and plays an important role in bone remodeling.
AB - Bone remodeling is critical to maintain the quality of bone tissues and to heal bone tissue injury. Osteoclasts and osteoblasts are special types of cells involved in this event. In particular, the resorption activity of mature osteoclasts is required for the formation of new bones. Human small leucine zipper protein (sLZIP) is known to induce the osteoblast differentiation of mesenchymal stem cells. However, the roles of sLZIP in osteoclast differentiation and bone remodeling have not been explored. In this study, we investigated the roles of sLZIP in regulating osteoclast formation and in the bone remodeling process using sLZIP transgenic (TG) mice. Tibiae from sLZIP TG mice contained more osteoclasts than those from wild type (WT) mice. Bone marrow-derived macrophages (BMM) from sLZIP TG mice showed increased differentiation into osteoclasts compared with BMM from WT mice. sLZIP bound to the promotor and induced the expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and its target osteoclastogenic genes. To understand the role of sLZIP in bone remodeling, a bone-defect model was generated. Results of micro-CT scanning and histologic analysis demonstrated that sLZIP TG mice have faster bone formation during healing compared with WT mice. Notably, the soft callus around the defect area was replaced faster by hard callus in sLZIP TG mice than in WT mice. These findings suggest that sLZIP promotes osteoclast differentiation and plays an important role in bone remodeling.
KW - Bone remodeling
KW - Fracture healing
KW - Osteoclast
KW - Transcription factor
KW - sLZIP
UR - http://www.scopus.com/inward/record.url?scp=85089844282&partnerID=8YFLogxK
U2 - 10.1016/j.bbamcr.2020.118827
DO - 10.1016/j.bbamcr.2020.118827
M3 - Article
C2 - 32822727
AN - SCOPUS:85089844282
SN - 0167-4889
VL - 1867
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 11
M1 - 118827
ER -