A single intra-articular injection of IDO-Gal3 shifts synovial fluid metabolic profiles for up to six weeks in male rats with knee instability.
| Title: | A single intra-articular injection of IDO-Gal3 shifts synovial fluid metabolic profiles for up to six weeks in male rats with knee instability. |
|---|---|
| Authors: | Patterson FM; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA; Pain Research and Intervention Center of Excellence, Clinical and Translational Science Institute, University of Florida, 2004 Mowry Rd, Gainesville, FL, 32610, USA. Electronic address: f.patterson@ufl.edu.; Cruz CJ; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA; Pain Research and Intervention Center of Excellence, Clinical and Translational Science Institute, University of Florida, 2004 Mowry Rd, Gainesville, FL, 32610, USA. Electronic address: cruzcarlos@ufl.edu.; Partain BD; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA. Electronic address: brittanypartain0112@gmail.com.; Welhaven H; Department of Chemistry and Biochemistry, Montana State University, 103 Chemistry and Biochemistry Building, Bozeman, MT, 59717, USA. Electronic address: hwelhaven@gmail.com.; Urrego Hernández E; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA; Research Service, Malcolm Randall Department of Veterans Affairs Medical Center, North, FL/South Georgia Veterans Health System, Mail Code 151, 1601 SW Archer Rd, Gainesville, FL, 32608, USA. Electronic address: estefani.urregoh@ufl.edu.; Breland A; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA. Electronic address: abreland@ufl.edu.; Griffith JL; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA. Electronic address: jlgriffith2018@gmail.com.; Wanchoo A; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA. Electronic address: awanchoo@bme.ufl.edu.; Cooper JO; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA. Electronic address: jonathancooper1@ufl.edu.; Yarrow JF; Research Service, Malcolm Randall Department of Veterans Affairs Medical Center, North, FL/South Georgia Veterans Health System, Mail Code 151, 1601 SW Archer Rd, Gainesville, FL, 32608, USA; Division of Endocrinology, Diabetes and Metabolism, College of Medicine, University of Florida, 1549 Gale Lemerand Dr, Gainesville, FL, 32610, USA; Brain Rehabilitation Research Center, Malcolm Randall Department of Veterans Affairs Medical Center, North, FL/South Georgia Veterans Health System, 1601 SW Archer Rd, Gainesville, FL, 32608, USA. Electronic address: joshua.yarrow@va.gov.; June RK; Department of Mechanical and Industrial Engineering, Montana State University, 220 Roberts Hall, Bozeman, MT, 59717, USA. Electronic address: rjune@montana.edu.; Keselowsky BG; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA. Electronic address: bkeselowsky@bme.ufl.edu.; Hudalla GA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA. Electronic address: ghudalla@bme.ufl.edu.; Allen KD; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Dr, JG56, Gainesville, FL, 32610, USA; Pain Research and Intervention Center of Excellence, Clinical and Translational Science Institute, University of Florida, 2004 Mowry Rd, Gainesville, FL, 32610, USA; Orthopaedics and Sports Medicine Institute, University of Florida, 3450 Hull Rd, Gainesville, FL, 32607, USA. Electronic address: kyle.allen@bme.ufl.edu. |
| Source: | Biochimie [Biochimie] 2026 Mar 18. Date of Electronic Publication: 2026 Mar 18. |
| Publication Model: | Ahead of Print |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 1264604 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1638-6183 (Electronic) Linking ISSN: 03009084 NLM ISO Abbreviation: Biochimie Subsets: MEDLINE |
| Imprint Name(s): | Publication: Paris : Editions Scientifiques Elsevier; Original Publication: Paris. |
| Abstract: | Joint metabolism is a potential therapeutic target space for osteoarthritis. We have previously developed a fusion protein of indoleamine 2,3-dioxygenase and galectin-3 (IDO-Gal3) to shift tryptophan metabolism toward the kynurenine pathway in the joint. Here, we hypothesized intra-articular IDO-Gal3 would prevent osteoarthritis progression in male rats as assessed via measures of pain-like behavior, synovial fluid metabolite profile, and joint structure. Joint degeneration was induced by medial collateral ligament transection and full or partial transection of the medial meniscus. IDO-Gal3 was delivered by a single intra-articular injection 3-4 days later. In the first cohort of Sprague Dawley rats, medial tibial plateau cartilage area increased following IDO-Gal3 treatment compared to saline (vehicle) treatment at four weeks. Hind paw withdrawal threshold was increased compared to vehicle control for four weeks. In the second cohort of Lewis rats, synovial fluid metabolomic profiles measured by LC-MS were altered in IDO-Gal3-treated rats at one week and six weeks. At one week, tryptophan metabolism pathway was altered in IDO-Gal3-treated animals. Amino acid pathways involved in collagen turnover, such as arginine and proline, were downregulated at six weeks in injured rats treated with IDO-Gal3. Energy metabolism pathways followed a similar trend. There was no change in medial tibial plateau cartilage area or percent trabecular bone area at six weeks, nor were there differences in bone microstructure, likely related to the partial medial meniscus transection. In conclusion, a single intra-articular injection of IDO-Gal3 improved tactile sensitivity and resulted in short- and long-term shifts in synovial fluid metabolic profiles.; (Copyright © 2026 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.) |
| Competing Interests: | Declaration of competing interest The University of Florida has pending patents related to molecules and their uses reported in this paper. Ronald K. June is a co-founder of OpenBioworks which was not involved in this study. Brittany D. Partain was employed at Exagen, Inc. and Jacob L. Griffith was employed at Medtronic following the completion of this study. Exagen, Inc. and Medtronic were not involved in this study. |
| Grant Information: | UC2 AR082196 United States AR NIAMS NIH HHS; R01 AR071431 United States AR NIAMS NIH HHS; S10 OD028650 United States OD NIH HHS; T32 AG049673 United States AG NIA NIH HHS; P20 GM103474 United States GM NIGMS NIH HHS |
| Contributed Indexing: | Keywords: Galectin-3; Indoleamine 2,3-dioxygenase; Intra-articular drug delivery; Knee osteoarthritis; Metabolomics |
| Entry Date(s): | Date Created: 20260320 Latest Revision: 20260421 |
| Update Code: | 20260421 |
| DOI: | 10.1016/j.biochi.2026.03.004 |
| PMID: | 41862150 |
| Database: | MEDLINE |
Journal Article