2. Academic Validation
  3. LMK-235 suppresses osteoclastogenesis and promotes osteoblastogenesis by inhibiting HDAC4

LMK-235 suppresses osteoclastogenesis and promotes osteoblastogenesis by inhibiting HDAC4

  • Sci Rep. 2024 Aug 28;14(1):19973. doi: 10.1038/s41598-024-70814-8.
Chongwei Chen # 1,  Yue Li # 2,  Teng Feng 1,  Xinping Chen 1,  Chengwei Li 1,  Lu Li 1,  Mengbo Zhu 3,  Yaqiong Chang 4,  Shaowei Wang 5
Affiliations

Affiliations

  • 1 Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.
  • 2 Department of Biochemistry, Basic Medical College of Shanxi Medical University, Taiyuan, People's Republic of China.
  • 3 Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China. coltzhu@163.com.
  • 4 Department of Nursing, The Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China. sxykdcyq@163.com.
  • 5 Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China. wangshaowei@sxmu.edu.cn.
  • # Contributed equally.
PMID: 39198677 DOI: 10.1038/s41598-024-70814-8
Abstract

Osteoblasts and osteoclasts play an important role in maintaining the structural integrity of bone tissue, in which osteoclasts degrade bone structure and osteoblasts restore bone tissue. The imbalance of osteoblast and osteoclast function can lead to many bone-related diseases, such as osteoporosis and inflammatory osteolysis. The drug that can both promote bone formation and inhibit bone loss will be able to treat those diseases. In this study, it was found that LMK-235, an selective HDAC4/5 inhibitor, inhibited the differentiation and maturation of osteoclasts by regulating NF-κB and p-Smad2/3 signaling pathways via inhibition of HDAC4. At the same time, we found that LMK-235 promoted osteoblast mineralization by upregulating Runx2 expression via inhibition of HDAC4. In vivo, LMK-235 was able to alleviate lipopolysaccharide (LPS)-induced calvarial osteolysis and promote the repair of bone defects. Taken together, LMK-235 suppresses osteoclast differentiation and promotes osteoblast formation by inhibiting HDAC4. This may provide a valuable treatment for bone diseases caused by abnormal osteoclast bone resorption and osteoblast bone regeneration.

Keywords

HDAC4; LMK-235; Osteoblast; Osteoclast; Osteolysis.

Figures
Products