Synovial fluid lubricin and hyaluronan are altered in equine osteochondral fragmentation, cartilage impact injury, and full-thickness cartilage defect models.
Abstract: The objectives of this study were to evaluate temporal changes in lubricin, hyaluronan (HA), and HA molecular weight (MW) distributions in three distinct models of equine joint injury affecting the carpal (wrist), tarsal (ankle), and femoropatellar (knee) joints. To establish ranges for lubricin, HA, and HA MW distributions across multiple joints, we first evaluated clinically healthy, high-motion equine joints. Synovial fluid was collected from high-motion joints in horses without clinical signs of joint disease (n = 11 horses, 102 joints) and from research horses undergoing carpal osteochondral fragmentation (n = 8), talar cartilage impact injury (n = 7), and femoral trochlear ridge full-thickness cartilage injury (n = 22) prior to and following arthroscopically induced joint injury. Lubricin and HA concentrations were measured via enzyme-linked immunosorbent assays, and gel electrophoresis was performed to evaluate HA MW distributions. Synovial fluid parameters were analyzed via linear regression models, revealing that lubricin and HA concentrations were conserved across healthy, high-motion joints. Lubricin concentrations increased post-injury in all osteoarthritis models (carpal fragmentation P = .001; talar impact P < .001; femoral trochlear ridge cartilage defect P = .03). Sustained loss of HA was noted post-arthroscopy following carpal osteochondral fragmentation (P < .0001) and talar impact injury (P < .001). Lubricin may be elevated to compensate for the loss of HA and to protect cartilage post-injury. Further investigation into the mechanisms regulating lubricin and HA following joint injury and their effects on joint homeostasis is warranted, including whether lubricin has value as a biomarker for post-traumatic osteoarthritis.
© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Publication Date: 2020-02-09 PubMed ID: 31965593PubMed Central: PMC7354223DOI: 10.1002/jor.24597Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- N.I.H.
- Extramural
- Biochemistry
- Biomarkers
- Cartilage
- Clinical Study
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Enzyme-Linked Immunosorbent Assay (ELISA)
- Equine Diseases
- Equine Health
- Horses
- Inflammation
- Injury
- Joint Health
- Laboratory Methods
- Molecular biology
- Osteoarthritis
- Physiology
- Synovial Fluid
- Veterinary Medicine
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research aimed to examine how lubricin and hyaluronan (HA), two key components of joint fluid, change in response to different types of joint injuries in horses. The findings indicate that lubricin levels increase following injury, potentially to compensate for loss of HA.
Research Context and Objectives
- This study aimed to evaluate the changes in concentrations of lubricin and hyaluronan (HA), and alterations in HA molecular weight following different types of joint injuries in horses. Three models representing different joint injuries affecting the wrist (carpal), ankle (tarsal), and knee (femoropatellar) were studied.
- Before commencing the study, the researchers evaluated healthy, high-motion joints in horses to establish a reference range for lubricin, HA, and HA molecular weight distributions.
Methodology
- Synovial fluid, the lubricating liquid in the joint cavities, was collected from 102 healthy joints without any signs of joint disease (from 11 horses), as well as from horses that had undergone three specific types of joint injury: carpal osteochondral fragmentation (8 horses), talar cartilage impact injury (7 horses), and femoral trochlear ridge full-thickness cartilage injury (22 horses).
- The study utilized arthroscopy, a minimally invasive surgical procedure, to induce the aforementioned joint injuries.
- The lubricin and HA concentrations in the collected synovial fluid were measured via enzyme-linked immunosorbent assays (ELISAs), a common lab technique used to measure the concentration of proteins in a solution. Meanwhile, gel electrophoresis was performed to evaluate HA molecular weight distributions.
Findings and Significance
- The researchers found that the concentrations of lubricin and HA were conserved across healthy, high-motion joints.
- After injury, lubricin concentrations increased in all the osteoarthritis models. Similarly, a sustained loss of HA was observed after arthroscopy in both carpal osteochondral fragmentation and talar impact injury cases.
- These results suggest that lubricin might be elevated to compensate for the loss of HA, aiming to protect the cartilage post-injury.
- This research calls for further investigation into the mechanisms regulating lubricin and HA following joint injury and how these changes impact joint health. More studies might also explore the potential of lubricin as a biomarker for post-traumatic osteoarthritis.
Cite This Article
APA
Peal BT, Gagliardi R, Su J, Fortier LA, Delco ML, Nixon AJ, Reesink HL.
(2020).
Synovial fluid lubricin and hyaluronan are altered in equine osteochondral fragmentation, cartilage impact injury, and full-thickness cartilage defect models.
J Orthop Res, 38(8), 1826-1835.
https://doi.org/10.1002/jor.24597 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
MeSH Terms
- Animals
- Female
- Glycoproteins / metabolism
- Horses
- Hyaluronic Acid / metabolism
- Joint Diseases / metabolism
- Joints / injuries
- Male
- Synovial Fluid / metabolism
Grant Funding
- K08 AR068469 / NIAMS NIH HHS
- P01 HL107147 / NHLBI NIH HHS
References
This article includes 50 references
- Anderson DD, Chubinskaya S, Guilak F, Martin JA, Oegema TR, Olson SA, Buckwalter JA. Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention.. J Orthop Res 2011 Jun;29(6):802-9.
- Furman BD, Mangiapani DS, Zeitler E, Bailey KN, Horne PH, Huebner JL, Kraus VB, Guilak F, Olson SA. Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis.. Arthritis Res Ther 2014 Jun 25;16(3):R134.
- Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis.. Ann N Y Acad Sci 2010 Mar;1192:230-7.
- Jay GD, Torres JR, Warman ML, Laderer MC, Breuer KS. The role of lubricin in the mechanical behavior of synovial fluid.. Proc Natl Acad Sci U S A 2007 Apr 10;104(15):6194-9.
- Jay GD, Elsaid KA, Zack J, Robinson K, Trespalacios F, Cha CJ, Chichester CO. Lubricating ability of aspirated synovial fluid from emergency department patients with knee joint synovitis.. J Rheumatol 2004 Mar;31(3):557-64.
- Marcelino J, Carpten JD, Suwairi WM, Gutierrez OM, Schwartz S, Robbins C, Sood R, Makalowska I, Baxevanis A, Johnstone B, Laxer RM, Zemel L, Kim CA, Herd JK, Ihle J, Williams C, Johnson M, Raman V, Alonso LG, Brunoni D, Gerstein A, Papadopoulos N, Bahabri SA, Trent JM, Warman ML. CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.. Nat Genet 1999 Nov;23(3):319-22.
- Jay GD, Torres JR, Rhee DK, Helminen HJ, Hytinnen MM, Cha CJ, Elsaid K, Kim KS, Cui Y, Warman ML. Association between friction and wear in diarthrodial joints lacking lubricin.. Arthritis Rheum 2007 Nov;56(11):3662-9.
- Rhee DK, Marcelino J, Al-Mayouf S, Schelling DK, Bartels CF, Cui Y, Laxer R, Goldbach-Mansky R, Warman ML. Consequences of disease-causing mutations on lubricin protein synthesis, secretion, and post-translational processing.. J Biol Chem 2005 Sep 2;280(35):31325-32.
- Ludwig TE, McAllister JR, Lun V, Wiley JP, Schmidt TA. Diminished cartilage-lubricating ability of human osteoarthritic synovial fluid deficient in proteoglycan 4: Restoration through proteoglycan 4 supplementation.. Arthritis Rheum 2012 Dec;64(12):3963-71.
- Antonacci JM, Schmidt TA, Serventi LA, Cai MZ, Shu YL, Schumacher BL, McIlwraith CW, Sah RL. Effects of equine joint injury on boundary lubrication of articular cartilage by synovial fluid: role of hyaluronan.. Arthritis Rheum 2012 Sep;64(9):2917-26.
- Kwiecinski JJ, Dorosz SG, Ludwig TE, Abubacker S, Cowman MK, Schmidt TA. The effect of molecular weight on hyaluronan's cartilage boundary lubricating ability--alone and in combination with proteoglycan 4.. Osteoarthritis Cartilage 2011 Nov;19(11):1356-62.
- Atarod M, Ludwig TE, Frank CB, Schmidt TA, Shrive NG. Cartilage boundary lubrication of ovine synovial fluid following anterior cruciate ligament transection: a longitudinal study.. Osteoarthritis Cartilage 2015 Apr;23(4):640-7.
- Elsaid KA, Fleming BC, Oksendahl HL, Machan JT, Fadale PD, Hulstyn MJ, Shalvoy R, Jay GD. Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury.. Arthritis Rheum 2008 Jun;58(6):1707-15.
- Teeple E, Elsaid KA, Fleming BC, Jay GD, Aslani K, Crisco JJ, Mechrefe AP. Coefficients of friction, lubricin, and cartilage damage in the anterior cruciate ligament-deficient guinea pig knee.. J Orthop Res 2008 Feb;26(2):231-7.
- Elsaid KA, Machan JT, Waller K, Fleming BC, Jay GD. The impact of anterior cruciate ligament injury on lubricin metabolism and the effect of inhibiting tumor necrosis factor alpha on chondroprotection in an animal model.. Arthritis Rheum 2009 Oct;60(10):2997-3006.
- Reesink HL, Watts AE, Mohammed HO, Jay GD, Nixon AJ. Lubricin/proteoglycan 4 increases in both experimental and naturally occurring equine osteoarthritis.. Osteoarthritis Cartilage 2017 Jan;25(1):128-137.
- Feeney E, Peal BT, Inglis JE, Su J, Nixon AJ, Bonassar LJ, Reesink HL. Temporal changes in synovial fluid composition and elastoviscous lubrication in the equine carpal fracture model.. J Orthop Res 2019 May;37(5):1071-1079.
- Grissom MJ, Temple-Wong MM, Adams MS, Tom M, Schumacher BL, McIlwraith CW, Goodrich LR, Chu CR, Sah RL. Synovial Fluid Lubricant Properties are Transiently Deficient after Arthroscopic Articular Cartilage Defect Repair with Platelet-Enriched Fibrin Alone and with Mesenchymal Stem Cells.. Orthop J Sports Med 2014 Jul;2(7).
- Ballard BL, Antonacci JM, Temple-Wong MM, Hui AY, Schumacher BL, Bugbee WD, Schwartz AK, Girard PJ, Sah RL. Effect of tibial plateau fracture on lubrication function and composition of synovial fluid.. J Bone Joint Surg Am 2012 May 16;94(10):e64.
- Neu CP, Reddi AH, Komvopoulos K, Schmid TM, Di Cesare PE. Increased friction coefficient and superficial zone protein expression in patients with advanced osteoarthritis.. Arthritis Rheum 2010 Sep;62(9):2680-7.
- Novakofski KD, Berg LC, Bronzini I, Bonnevie ED, Poland SG, Bonassar LJ, Fortier LA. Joint-dependent response to impact and implications for post-traumatic osteoarthritis.. Osteoarthritis Cartilage 2015 Jul;23(7):1130-7.
- Cushnaghan J, Dieppe P. Study of 500 patients with limb joint osteoarthritis. I. Analysis by age, sex, and distribution of symptomatic joint sites.. Ann Rheum Dis 1991 Jan;50(1):8-13.
- Kawcak CE. Biomechanics in joints. 2016.
- McCoy AM. Animal Models of Osteoarthritis: Comparisons and Key Considerations.. Vet Pathol 2015 Sep;52(5):803-18.
- McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res 2012 Nov;1(11):297-309.
- Penell JC, Egenvall A, Bonnett BN, Olson P, Pringle J. Specific causes of morbidity among Swedish horses insured for veterinary care between 1997 and 2000.. Vet Rec 2005 Oct 15;157(16):470-7.
- Delco ML, Bonnevie ED, Alexander PG. An in vivo large animal model to study impact-induced cartilage injury and the development of early posttraumatic ankle osteoarthritis. Osteoarthritis Cartilage 25:s309–310.
- Nixon AJ, Sparks HD, Begum L, McDonough S, Scimeca MS, Moran N, Matthews GL. Matrix-Induced Autologous Chondrocyte Implantation (MACI) Using a Cell-Seeded Collagen Membrane Improves Cartilage Healing in the Equine Model.. J Bone Joint Surg Am 2017 Dec 6;99(23):1987-1998.
- Lee HG, Cowman MK. An agarose gel electrophoretic method for analysis of hyaluronan molecular weight distribution.. Anal Biochem 1994 Jun;219(2):278-87.
- Preibisch S, Saalfeld S, Tomancak P. Globally optimal stitching of tiled 3D microscopic image acquisitions.. Bioinformatics 2009 Jun 1;25(11):1463-5.
- Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A. Fiji: an open-source platform for biological-image analysis.. Nat Methods 2012 Jun 28;9(7):676-82.
- Ogawa H, Matsumoto K, Terabayashi N, Kawashima K, Takeuchi K, Akiyama H. Association of lubricin concentration in synovial fluid and clinical status of osteoarthritic knee.. Mod Rheumatol 2017 May;27(3):489-492.
- Ogawa H, Kozhemyakina E, Hung HH, Grodzinsky AJ, Lassar AB. Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways.. Genes Dev 2014 Jan 15;28(2):127-39.
- Jones AR, Chen S, Chai DH, Stevens AL, Gleghorn JP, Bonassar LJ, Grodzinsky AJ, Flannery CR. Modulation of lubricin biosynthesis and tissue surface properties following cartilage mechanical injury.. Arthritis Rheum 2009 Jan;60(1):133-42.
- Nugent GE, Aneloski NM, Schmidt TA, Schumacher BL, Voegtline MS, Sah RL. Dynamic shear stimulation of bovine cartilage biosynthesis of proteoglycan 4.. Arthritis Rheum 2006 Jun;54(6):1888-96.
- Zhang D, Johnson LJ, Hsu HP, Spector M. Cartilaginous deposits in subchondral bone in regions of exposed bone in osteoarthritis of the human knee: histomorphometric study of PRG4 distribution in osteoarthritic cartilage.. J Orthop Res 2007 Jul;25(7):873-83.
- Hempfling H. Intra-articular hyaluronic acid after knee arthroscopy: a two-year study.. Knee Surg Sports Traumatol Arthrosc 2007 May;15(5):537-46.
- de Rezende MU, de Campos GC. VISCOSUPPLEMENTATION.. Rev Bras Ortop 2012 Mar-Apr;47(2):160-4.
- Teeple E, Karamchedu NP, Larson KM, Zhang L, Badger GJ, Fleming BC, Jay GD. Arthroscopic irrigation of the bovine stifle joint increases cartilage surface friction and decreases superficial zone lubricin.. J Biomech 2016 Sep 6;49(13):3106-3110.
- Cowman MK, Lee HG, Schwertfeger KL, McCarthy JB, Turley EA. The Content and Size of Hyaluronan in Biological Fluids and Tissues.. Front Immunol 2015;6:261.
- Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2.. J Immunol 2006 Jul 15;177(2):1272-81.
- Iacob S, Knudson CB. Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes.. Int J Biochem Cell Biol 2006 Jan;38(1):123-33.
- Rivas F, Zahid OK, Reesink HL, Peal BT, Nixon AJ, DeAngelis PL, Skardal A, Rahbar E, Hall AR. Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor.. Nat Commun 2018 Mar 12;9(1):1037.
- Rinnovati R, Bonelli F, Tognetti R. Effect of repeated arthrocentesis on cytology of synovial fluid. J Equine Vet Sci 57:112–115.
- van den Boom R, van de Lest CH, Bull S, Brama RA, van Weeren PR, Barneveld A. Influence of repeated arthrocentesis and exercise on synovial fluid concentrations of nitric oxide, prostaglandin E2 and glycosaminoglycans in healthy equine joints.. Equine Vet J 2005 May;37(3):250-6.
- Tulamo RM, Heiskanen T, Salonen M. Concentration and molecular weight distribution of hyaluronate in synovial fluid from clinically normal horses and horses with diseased joints.. Am J Vet Res 1994 May;55(5):710-5.
- Ai M, Cui Y, Sy MS, Lee DM, Zhang LX, Larson KM, Kurek KC, Jay GD, Warman ML. Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints.. PLoS One 2015;10(2):e0116237.
- Svala E, Jin C, Rüetschi U, Ekman S, Lindahl A, Karlsson NG, Skiöldebrand E. Characterisation of lubricin in synovial fluid from horses with osteoarthritis.. Equine Vet J 2017 Jan;49(1):116-123.
- Lanovaz JL, Khumsap S, Clayton HM, Stick JA, Brown J. Three-dimensional kinematics of the tarsal joint at the trot.. Equine Vet J Suppl 2002 Sep;(34):308-13.
- Lee H, Kirkland WG, Whitmore RN, Theis KM, Young HE, Richardson AJ, Jackson RL, Hanson RR. Comparison of equine articular cartilage thickness in various joints.. Connect Tissue Res 2014 Oct-Dec;55(5-6):339-47.
Citations
This article has been cited 11 times.- Du J, Zhu Z, Liu J, Bao X, Wang Q, Shi C, Zhao C, Xu G, Li D. 3D-printed gradient scaffolds for osteochondral defects: Current status and perspectives. Int J Bioprint 2023;9(4):724.
- Dilley JE, Everhart JS, Klitzman RG. Hyaluronic acid as an adjunct to microfracture in the treatment of osteochondral lesions of the talus: a systematic review of randomized controlled trials. BMC Musculoskelet Disord 2022 Apr 2;23(1):313.
- Watkins A, Fasanello D, Stefanovski D, Schurer S, Caracappa K, D'Agostino A, Costello E, Freer H, Rollins A, Read C, Su J, Colville M, Paszek M, Wagner B, Reesink H. Investigation of synovial fluid lubricants and inflammatory cytokines in the horse: a comparison of recombinant equine interleukin 1 beta-induced synovitis and joint lavage models. BMC Vet Res 2021 May 12;17(1):189.
- Noordwijk KJ, Qin R, Diaz-Rubio ME, Zhang S, Su J, Mahal LK, Reesink HL. Metabolism and global protein glycosylation are differentially expressed in healthy and osteoarthritic equine carpal synovial fluid. Equine Vet J 2022 Mar;54(2):323-333.
- Watkins AR, Reesink HL. Lubricin in experimental and naturally occurring osteoarthritis: a systematic review. Osteoarthritis Cartilage 2020 Oct;28(10):1303-1315.
- Secor EJ, Womack SJ, Ysebaert MP, Colville MJ, Reesink HL. Synovial fluid alpha-2-macroglobulin, gelsolin and lubricin distinguish between osteoarthritic and healthy equine joints. Equine Vet J 2026 Jan;58(1):49-59.
- Riley JW, Chance LM, Barshick MR, Johnson SE. Administration of sodium hyaluronate to adult horses prior to and immediately after exercise does not alter the range of motion in either the tarsus or metacarpophalangeal joints. Transl Anim Sci 2024;8:txae153.
- Chalidapong P, Vaseenon T, Chattipakorn N, Chattipakorn SC. Potential Roles of Inflammation on Post-Traumatic Osteoarthritis of the Ankle. Int J Mol Sci 2024 May 28;25(11).
- Kraus VB, Hsueh MF. Molecular biomarker approaches to prevention of post-traumatic osteoarthritis. Nat Rev Rheumatol 2024 May;20(5):272-289.
- Chan DD, Guilak F, Sah RL, Calve S. Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues. Annu Rev Biomed Eng 2024 Jul;26(1):25-47.
- Wang Y, Gludish DW, Hayashi K, Todhunter RJ, Krotscheck U, Johnson PJ, Cummings BP, Su J, Reesink HL. Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture. Sci Rep 2020 Oct 7;10(1):16725.
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