2. Academic Validation
  3. Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells

Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells

  • Commun Biol. 2025 Feb 26;8(1):310. doi: 10.1038/s42003-025-07765-x.
Chuan Li # 1 2,  Jiahui Long # 1,  Shuqing Chen # 3,  Liru Tian 1 4,  Ya Xiao 1,  Shulin Chen 1,  Deying Su 1,  Baolin Zhang 5,  Peiqiang Su 6,  Liao Zhiheng 7,  Caixia Xu 8
Affiliations

Affiliations

  • 1 Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China.
  • 2 Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, 510260 Guangzhou, China.
  • 3 Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2 Rd., No. 58, Yuexiu District, 510080 Guangzhou, China.
  • 4 Department of Pathology, Sun Yat-sen University Cancer Center, 510062 Guangzhou, China.
  • 5 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China.
  • 6 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China. supq@mail.sysu.edu.cn.
  • 7 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China. liaozhh27@mail.sysu.edu.cn.
  • 8 Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China. xucx3@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 40000807 DOI: 10.1038/s42003-025-07765-x
Abstract

The lineage commitment and differentiation of mesenchymal stem cells (MSCs) play a crucial role in bone homeostasis. MAPK7 (Mitogen-activated protein kinase 7), a member of MAPK Family, controls cell differentiation, proliferation and survival. However, the specific role of Mapk7 in regulating osteogenic and adipogenic differentiation of MSCs remains to be determined. In this study, depletion of Mapk7 in MSCs by crossing Prx1-Cre mice to Mapk7flox/flox resulted in severe low bone mass and accumulation of fat in bone marrow exhibiting osteoporosis (OP) in mice. Mapk7 promoted osteogenic differentiation and inhibited adipogenic differentiation of MSCs after knocking out and over-expressing Mapk7 in vitro. Mechanistically, Mapk7 activated Wnt/β-catenin signaling by phosphorylating Lrp6 at Ser1490, which ultimately enhanced osteogenesis and suppressed adipogenesis of MSCs. This is of great clinical and scientific significance for understanding biological function of Mapk7 and developing potential therapeutic targets for treatment of MSCs differentiation imbalance related bone diseases, such as, osteoporosis.

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