In this subsection of our Preclinical Press newsletter, we love to highlight exciting topics and scientists from the field of comparative medicine to foster translational science.

Proteomics Reveals Increased Periostin in Synovial Fluid from Canine and Human Anterior Cruciate Ligament Injury
Author: Lynn Pezzanite, DVM, PhD

Posttraumatic osteoarthritis (PTOA) occurs commonly following anterior cruciate ligament (ACL) injury in both dogs and humans, frequently affecting young athletic patients. While ACL reconstruction in people has been associated with less severe radiographic changes compared to nonsurgical interventions, factors contributing to development and progression of PTOA following ACL injury remain poorly understood. To address this gap, researchers at Cornell University College of Veterinary Medicine, University of California, Davis School of Veterinary Medicine, and Weill Cornell Medical College and Hospital for Special Surgery, New York – led by Heidi Reesink, VMD, PhD, Diplomate American College of Veterinary Surgeons and Scott Rodeo, MD – evaluated differentially expressed proteins that may serve as candidate biomarkers or potential therapeutic targets to define disease pathogenesis further following ACL injury using the naturally occurring canine model. Like humans, dogs frequently develop PTOA after ACL injury, share environment, lifestyle and other risk factors such as obesity with humans, and undergo similar imaging, surgery and medical procedures following injury. Obtaining control synovial fluid samples from clinically healthy dogs may also be more feasible than in humans, lending further advantage to the translational study of disease processes in canines. Improved understanding of pathophysiology of PTOA following ACL injury is critical to identify methods to delay progression in both human and veterinary species. Identification of conserved targets across species may hasten biomarker identification and therapeutic development.

In this study, synovial fluid (SF) samples were collected from human and canine knees with ACL injury or control knees to identify proteins with differential abundance in ACL injury. The SF proteome was evaluated using nano-scale reverse-phase chromatography and tandem mass spectrometry and associations between proteins and ACL injury analyzed. Immunoassays were then used to validate key proteins identified via mass spectrometry, including periostin, alpha-2-macroglobulin (A2M) and lubricin, in additional SF samples. Periostin was the most upregulated SF protein in both dogs and humans with ACL injury which was supported by ELISA validation. Other proteins, including A2M and apoliprotein B-100, were strongly upregulated in both species, while vimentin and hemoglobin subunit were strongly downregulated. Approximately 60% of proteins detected were shared between species, and immunoregulatory and macromolecular transport proteins were the most common families.

These findings support using dogs with cranial cruciate ligament injury as a clinically relevant spontaneous animal model for human ACL injury and identified periostin as a possible biomarker or therapeutic target for future investigation in both species. Using a One Health approach to identify commonalities in disease processes across species has been proposed as a strategy to enable more efficient and robust biomarker identification and therapeutic development. This study provides an example where use of multispecies proteomics data resulted in identification of conserved SF protein targets across species. Future studies will investigate mechanisms that lead to increased SF periostin following ACL injury and differentiate whether periostin is simply a biomarker for ACL injury or if periostin plays an active role in PTOA pathophysiology and progression.

Reference: Womack SJ, Carballo CB, Secor EJ, Rodeo SA, Reesink HL. Proteomics Reveals Increased Periostin in Synovial Fluid From Canine and Human Anterior Cruciate Ligament Injury. J Orthop Res. 2025 Jul;43(7):1239-1249. doi: 10.1002/jor.26078. Epub 2025 Apr 17. PMID: 40247443; PMCID: PMC12159583.