Impairment of Bone Remodeling in LIGHT/TNFSF14-Deficient Mice (original) (raw)

Abstract

Multiple cytokines produced by immune cells induce remodeling and aid in maintaining bone homeostasis through differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. Here, we investigate bone remodeling controlled by the tumor necrosis factor (TNF) superfamily cytokine LIGHT. LIGHT-deficient mice (Tnfsf14-/- ) exhibit spine deformity and reduced femoral cancellous bone mass associated with an increase in the osteoclast number and a slight decrease of osteoblasts compared with WT mice. The effect of LIGHT in bone cells can be direct or indirect, mediated by both the low expression of the anti-osteoclastogenic osteoprotegerin (OPG) in B and T cells and reduced levels of the pro-osteoblastogenic Wnt10b in CD8+ T cells in Tnfsf14-/- mice. LIGHT stimulation increases OPG levels in B, CD8+ T, and osteoblastic cells, as well as Wnt10b expression in CD8+ T cells. The high bone mass in Light and T- and B-cell-deficient mice (Rag- /Tnfsf14- ) supports the cooperative role ...

Key takeaways

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  1. LIGHT deficiency in Tnfsf14-/- mice leads to increased osteoclastogenesis and reduced bone mass.
  2. Approximately 40% of Tnfsf14-/- mice exhibit spinal deformities due to impaired bone remodeling.
  3. LIGHT regulates bone homeostasis by modulating OPG and Wnt10b expression in T and B cells.
  4. Rag-/Tnfsf14- double knockout mice show a 33% increase in trabecular bone volume compared to Tnfsf14-/- mice.
  5. The study reveals the immune system's critical role in skeletal physiology and potential therapeutic avenues.

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FAQs

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What key morphological changes occur in Tnfsf14-/- mice bone structure?add

Tnfsf14-/- mice show a 40% spinal deformity and significant reductions in femoral cancellous bone area.

How does LIGHT deficiency affect osteoclastogenesis in Tnfsf14-/- mice?add

Tnfsf14-/- mice display increased osteoclast formation and activity, correlating with higher histological TRAP-stained OC counts.

What is the impact of LIGHT on OPG and RANKL expression?add

In Tnfsf14-/- mice, OPG levels decrease significantly while RANKL levels remain unchanged, increasing the RANKL/OPG ratio.

How do immune cells contribute to bone homeostasis in Tnfsf14-/- mice?add

Reduced OPG production from CD8+ T and IgM+ B cells disrupts bone homeostasis in Tnfsf14-/- models.

What experimental methods assess bone structure in this study?add

The study employs microCT, histological staining, and dynamic histomorphometry with calcein and xylenol orange for analysis.