Activation of 4-1BB signaling in bone marrow stromal cells triggers bone loss via the p-38 MAPK-DKK1 axis in aged mice

This study investigates the causes of bone loss in old age, focusing on bone marrow stromal cells (BMSCs). They found that a signaling pathway involving 4-1BB is more active in the bone marrow of older mice. The increased 4-1BB activity reduces the ability of BMSCs to form new bone through the p38 MAPK-Dkk1 pathway. Blocking this 4-1BB pathway can prevent bone loss in older mice. This research helps us understand how age-related bone loss happens and suggests new ways to treat osteoporosis by targeting the 4-1BB signaling pathway.

• 1
  4-1BB is upregulated in BMSCs from aged mice, which leads to the attenuation of osteogenic differentiation potential via the p38 MAPK-Dkk1 pathway.
• 2
  Trabecular bone loss in aged mice can be rescued by blocking 4-1BB signaling in vivo.
• 3
  The accumulation of 4-1BB and 4-1BBL in bone marrow contributes to bone loss in aged mice.