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Sundaram V et al. ACL, Meniscal, and Cartilage Injuries Are Associated With Distinct Synovial Fluid Biomarker Profiles. AJSM 2025. PMID: 41055107

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This study examined whether different knee injuries are linked to distinct synovial fluid biomarker patterns at the time of arthroscopic surgery. Researchers prospectively enrolled 387 patients undergoing knee arthroscopy and measured 10 inflammatory and repair-related biomarkers in synovial fluid collected before incision. Patients had ACL injury, meniscal injury, cartilage damage, or combinations of these.

Using principal component analysis, the team identified three main biomarker clusters explaining 66.9% of the variation.  
- <strong>PC1</strong> reflected a <strong>pro-inflammatory profile</strong> and included VEGF, IL-6, MMP-3, MIP-1b, and MCP-1.  
- <strong>PC2</strong> reflected an <strong>anti-inflammatory profile</strong> and included TIMP-1 and TIMP-2.  
- <strong>PC3</strong> was a <strong>mixed profile</strong> involving RANTES, bFGF, and IL-1Ra.

In multivariable analysis, <strong>ACL injury and meniscal injury were positively associated with the pro-inflammatory PC1</strong>, while <strong>more severe cartilage damage was negatively associated with the anti-inflammatory PC2</strong>. ACL injury was also associated with PC3. Importantly, <strong>PC1 was linked to worse baseline knee function</strong> on the Lysholm score, suggesting that stronger pro-inflammatory signaling corresponds with poorer symptoms and function.

The authors conclude that <strong>cartilage lesions have a synovial fluid inflammatory profile distinct from ACL and meniscal injuries</strong>. ACL and meniscal injuries tend to produce a pro-inflammatory environment, whereas cartilage damage is associated with reduced anti-inflammatory signaling. These findings improve understanding of how different knee injuries influence joint inflammation and may help guide future injury-specific treatments aimed at preventing posttraumatic osteoarthritis.

Keywords

knee injury

synovial fluid biomarkers

arthroscopic surgery

ACL injury

meniscal injury

cartilage damage

inflammation

principal component analysis

pro-inflammatory profile

posttraumatic osteoarthritis