Journal Club: Loss of OSBPL2 lead to impairment of the barrier function of the small blood vessels: implication for DFNA hearing loss caused by OSBPL2 variants.

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Today's journal article

Yang Q, Li T, Lu Y, Wang T, Chen Z, Xing G, Wei Q, Cao X, Yao J. OSBPL2 deficiency impaired cochlear blood-labyrinth barrier via activation of NF-κB signaling pathway. 

Why I picked this article

There are many genes identified to be responsible for genetic hearing loss in humans. The gene for oxysterol-binding protein like 2, OSBPL2, is a gene previously linked to autosomal dominant non-syndromic hearing loss (DFNA). The protein product of the gene, OSBPL2, is known to regulate bioprocesses of cells that involve lipids. But how exactly mutations in this gene cause hearing problems hasn't been well understood. 

In this regard, this research focuses on structures, the stria vascularis and its associated blood-labyrinth barrier (BLB), important for homeostasis of the cochlea. The stria vascularis is an area of the cochlea important for generating a very special ionic environment in the cochlea. The stria vascularis is rich in small blood vessels with special barriers called the blood-labyrinth barrier, which, like the blood-brain barrier, keeps harmful substances out while maintaining the delicate ion environment essential for hearing. 

This study investigates how OSBPL2 malfunction lead to sensorineural hearing loss with focus on the stria vascularis.  

Some of the research findings

Animal and cell culture model: 

  • Osbpl2-knockout  Osbpl2-KO mice
  • Control mice = age-matched wild-type C57BL/6 J mice
  • Human umbilical vein endothelial cells were cultured. 

Change in blood vessels and inflammation:

  • Fluorescent dyes (FITC-dextran) were injected into the mouse tail vein, and 1 hour later, cochleae were fixed and processed for microscopy. Blood vessels were visualised with fluorescent tomato lectin. 
  • Proteins responsible for the barrier function of blood-labyrinth barrier was assessed by microscopy (ZO-1, occludin)
  • The level of inflammation was assessed by looking at RNA or protein levels of inflammation-related signalling molecules (TNF-α, IL-1β and NF-κB, etc).  

Findings:

  • OSBPL2 protein is found in cells of the stria vascularis. 
  • OSBPL2-knockout mice at 6 months and 10 months of ages, showed leakiness in the small blood vessels (capillaries). Some proteins important for barrier functions of the blood vessels were also decreased. 
  • When you artificially lowered the amount of OSBPL2 in cultured human umbilical endothelial cells, the barrier proteins (Zo-1) decreased, and the leakiness of the cells increased. 
  • In both the OSBL2-knockout mouse model and in human cultured cells, OSBL2 deficiency increased signs of inflammation and increased apoptotic cell death. 
From part of Figure 1A. Leaky blood vessels in 10-month old OSBPL2 knock-out mouse cochlea. Green is the dye leaked from the blood vessel, and red labels the blood vessels. Yang et al. (2025).

Taken together, researchers suggest that OSBPL2 deficiency "induced cochlear inflammation and SV apoptosis via NF-κB signaling pathway, contributed to the disruption of TJs in SV, and eventually posed harm to BLB structure and function."

Haruna's takeaway

We often think about hearing loss in terms of hair cells and neurons, but this study points to the barrier systems that protect the cochlear environment. The blood-labyrinth barrier is essential for keeping the right ions and substances inside the cochlea and protecting against toxins or immune cells that could disrupt hearing. The idea that a lipid-binding protein like OSBPL2 could regulate barrier integrity via tight junction maintenance adds a new dimension to the potential pathologies behind genetic hearing loss. The pathology around labyrinthitis also links in with our interest in blood vessels, and I look forward to our research getting out there. 

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This is Haruna's 42/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.