Functional Loss of Terminal Complement Complex Protects Rabbits from Injury-Induced Osteoarthritis on Structural and Cellular Level

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2023 Feb 25

PMID 36830586

Authors

Jana Riegger

Helga Joos

Valentin Mohler

Frank Leucht

Katrin Rading

Christian Kubisch

Anita Ignatius

Markus Huber-Lang

Rolf E Brenner

Affiliations

Soon will be listed here.

Abstract

The terminal complement complex (TCC) has been described as a potential driver in the pathogenesis of posttraumatic osteoarthritis (PTOA). However, sublytic TCC deposition might also play a crucial role in bone development and regeneration. Therefore, we elucidated the effects of TCC on joint-related tissues using a rabbit PTOA model. In brief, a C6-deficient rabbit breed was characterized on genetic, protein, and functional levels. Anterior cruciate ligament transection (ACLT) was performed in C6-deficient (C6) and C6-sufficient (C6) rabbits. After eight weeks, the progression of PTOA was determined histologically. Moreover, the structure of the subchondral bone was evaluated by µCT analysis. C6 deficiency could be attributed to a homozygous 3.6 kb deletion within the C6 gene and subsequent loss of the C5b binding site. Serum from C6 animals revealed no hemolytic activity. After ACLT surgery, joints of C6 rabbits exhibited significantly lower OA scores, including reduced cartilage damage, hypocellularity, cluster formation, and osteophyte number, as well as lower chondrocyte apoptosis rates and synovial prostaglandin E2 levels. Moreover, ACLT surgery significantly decreased the trabecular number in the subchondral bone of C6 rabbits. Overall, the absence of TCC protected from injury-induced OA progression but had minor effects on the micro-structure of the subchondral bone.

Citing Articles

Terminal complement complex deposition on chondrocytes promotes premature senescence in age- and trauma-related osteoarthritis.

Ruths L, Hengge J, Teixeira G, Haffner-Luntzer M, Ignatius A, Riegger J Front Immunol. 2025; 15:1470907.

PMID: 39877352 PMC: 11772281. DOI: 10.3389/fimmu.2024.1470907.

Analysis of Intervertebral Disc Degeneration Induced by Endplate Drilling or Needle Puncture in Complement C6-Sufficient and C6-Deficient Rabbits.

Kuhn A, Huber-Lang M, Weckbach S, Riegger J, Teixeira G, Rasche V Biomedicines. 2024; 12(8).

PMID: 39200157 PMC: 11351780. DOI: 10.3390/biomedicines12081692.

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