bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.01.05.697672

Subchondral H-type Blood Vessel Formation Aggravates Articular Cartilage Degeneration through LEP-LEPR Axis

Yu, C.·Qin, J.·Zhao, X.·Luo, S.·Zeng, H.·Xu, B.·Li, J.
View original source ↗Export metadata ↓

Abstract

BackgroundOsteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage deterioration that has resulted in severe physical and economic costs for society. Risk factors for osteoarthritis encompass genetic predisposition, mechanical influences, obesity, inflammation, and metabolic problems. Recent reports indicate that the morphological alterations of subchondral bone evolve dynamically with the advancement of osteoarthritis. A significant alteration in subchondral bone is the development of aberrant blood vessels, particularly H-type vessels. H-type arteries are essential for preserving subchondral bone homeostasis. They support nutrients and oxygen to bone tissue and eliminate waste, thereby supporting the metabolic activities of osteoblasts and osteoclasts. However, the upstream factors governing H-type arteries are yet unknown. MethodsThe whole transcriptome analysis was performed by informatics which is further verified in clinical samples. Using LEP and LEPR knockout mice, the correlation between abnormal subchondral bone metabolism and LEP, LEPR, and H-type vessel formation were uncovered. ConclusionsThis study reveals that the lipid metabolism pathway was highly enriched on the OA lesion, and LEP and LEPR were markedly underexpressed in the subchondral bone on the side with severe OA lesions. The causal relationship of the LEP-LEPR-CD31 signalling pathway in aging and osteoarthritis models is revealed at the overall and molecular levels. This project will provide a new theoretical basis for the pathogenesis of early OA and new ideas and targets for the clinical treatment of OA by exploring the LEP-LEPR-CD31 signalling in osteoarthritis.

Source connections

Explore related subjects

pathologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yu, C., Qin, J., Zhao, X., Luo, S., Zeng, H., Xu, B., Li, J.. 2026-01-05. Subchondral H-type Blood Vessel Formation Aggravates Articular Cartilage Degeneration through LEP-LEPR Axis. https://doi.org/10.64898/2026.01.05.697672

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Autophagic flux is increased in peripheral blood mononuclear cells in atherosclerotic vascular disease and associates inversely with adverse cardiovascular events

Background: Autophagy is a homeostatic pathway supporting stress adaptation and is dysregulated in atherosclerosis. Its potential as a biomarker or therapeutic target in atherosclerotic vascular disease (ASVD) remains incompletely defined. We measured autophagic flux in peripheral blood mononuclear cells (PBMCs) from patients with peripheral arterial disease (PAD) or carotid stenosis (CS), compared with healthy controls, and explored clinical outcome associations. Methods: Ninety-four patients with PAD or CS and 19 healthy controls were studied. Autophagic flux was quantified from fresh blood using a validated ex vivo chloroquine inhibition ELISA measuring LC3BII accumulation. Major adverse cardiovascular events (MACE) and major adverse limb events (MALE) were ascertained over a median follow up of 828 days. Results: The ASVD cohort comprised claudication (n = 16), chronic limb threatening ischemia (CLTI; n = 49), and CS (n = 29). Autophagic flux was higher in ASVD than controls (mean 281.4 vs. 182.3 ng LC3BII/mg protein/h; p < 0.0001) and remained independently associated after multivariable adjustment. Within CLTI, concurrent infection was associated with lower flux (p = 0.001), approaching control levels (p = 0.327). In CLTI, higher flux quartiles were associated with lower MACE risk, most strongly for quartile 3 (hazard ratio 0.07 vs. quartile 1, 95% CI 0.01 to 0.50; p = 0.009). Conclusion: Autophagic flux is elevated in PBMCs from ASVD patients, independent of age and sex. Attenuated flux in CLTI with concurrent infection may indicate autophagic exhaustion in advanced disease. The association between higher flux and lower MACE in CLTI suggests prognostic utility, warranting evaluation in larger prospective studies.

pathology↗
bioRxiv2026

Quantitative Model of the Ocular Immune Response during Seasonal Allergic Conjunctivitis

Allergic conjunctivitis is an inflammation of the conjunctiva caused by allergen; it is common disorder affecting up to 40% of the population. In this work, we study seasonal allergic conjunctivitis (SAC), also called "hay fever eyes", which is caused by exposure to airborne pollens. We develop a mathematical model quantifying the ocular immune system response to the allergens. First, we present a simplified qualitative description of the immunopathogenesis of SAC. Then, we express each chosen immunopathological mechanism mathematically to construct a system of thirty-one ordinary differential equations. We compare summary statistics of the predicted observable immune signals to experimental measurements and find our model captures key qualitative features of SAC progression. We then compare our predicted time series of histamine concentration to symptom scores and find a strong correlation suggesting the model predicts relevant clinically trends. Next, we calibrate the model through multi-step process. We find the most influential parameters are the production and depletion rates of IL-4, and the production rates of IL-5 and IL-8. These cytokines are targeted in treatments for asthma, atopic dermatitis, and severe eosinophilic associated disorder and suggest potential therapeutic targets for SAC. Our calibrated model mimics most of the summary statistics of the experimentally observable immune signals with discrepancies for IL-5 and IL-13 indicating that additional immunopathological mechanisms could be important.

pathology↗
bioRxiv2026

Dysregulated Platelet GPIb alpha - VWF Signalling in Abdominal Aortic Aneurysm formation and Progression

Background: Platelets are critical drivers of thrombo-inflammatory responses in different cardiovascular diseases. Abdominal aortic aneurysm (AAA) is a progressive, life-threatening vascular disorder mainly characterised by chronic inflammation, extracellular matrix degradation, and the formation of a platelet-rich intraluminal thrombus (ILT). Experimental and clinical evidence identified platelets as main players in AAA pathology as evidenced by elevated platelet activation and procoagulant activity that critically contribute to AAA progression. Methods: The present study investigated the contribution of glycoprotein (GP)Ib alpha, the von Willebrand factor (VWF)-binding subunit of the platelet GPIb-IX-V complex, to AAA initiation and progression in experimental AAA using the ePPE mouse model and in patients. Results: Genetic ablation of platelet GPIb alpha significantly attenuated early aneurysm expansion in experimental AAA, indicating a critical role for GPIb alpha during the initial stages of aneurysm development. This initial effect was compensated at later time points showing no differences in aneurysm progression between groups. Notably, genetic deletion of GPIb alpha induced a constitutively hyperactive platelet phenotype already in naive mice that was further amplified during experimental AAA. This elevated platelet hyperactivity was mainly due to increased GPVI activation of platelets 28 days post-surgery. To assess the clinical relevance, spatial profiles of human ILT specimens from patients with AAA were analysed. In the ILT, we detected a highly compartmentalised distribution of GPIb alpha and VWF with pronounced enrichment within the luminal layer. In parallel, circulating VWF activity as well as platelet surface expression of GPIb alpha were significantly increased in patients with AAA. Conclusion: Collectively, these findings identify a dysregulated GPIb alpha-VWF axis in human AAA pathology, mainly characterised by enhanced platelet GPIb alpha surface expression and increased activity of circulating VWF.

pathology↗