Download PDF
Vet Comp Orthop Traumatol 2022; 35(02): 090-095
DOI: 10.1055/s-0041-1736189
Original Research

Intra-Articular Administration of a Synthetic Lubricin in Canine Stifles

Kei Hayashi
1   College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
,
Alexandria Bourgeois
1   College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
,
Daniel Lopez 
1   College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
,
Brian G. Caserto
2   VetPath Services, Stone Ridge, New York, United States
,
Erin Berthelsen
1   College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
,
Ursula Krotscheck
1   College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
,
Heidi L. Reesink
1   College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
,
Sun Young Kim 
3   Purdue University College of Veterinary Medicine, West Lafayette, Indiana, United States
,
David Putnam
4   Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, United States
5   Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, United States
› Author Affiliations Funding This study was supported by Center for Advanced Technology (CAT), State of New York and the National Institutes of Health under Award Number R01 AR066667 (to DP). This work made use of the Cornell Center for Materials Research Facilities supported by the National Science Foundation under Award Number DMR-1719875.
› Further Information
    Permissions and Reprints

Abstract

Objective The aim of this study was to evaluate the functional, systemic, synovial and articular changes after intra-articular administration of a synthetic lubricin within healthy canine stifles.

Study Design A prospective randomized blinded placebo-controlled study composed of 10 dogs equally divided into either a treatment group (intra-articular synthetic lubricin injection, n = 5) or control group (saline, n = 5). Clinical (orthopaedic examination, gait observation, gait analysis), biochemical (complete blood count and biochemistry profile) and local tissue outcomes (joint fluid analysis, joint capsule and articular cartilage histopathology) were evaluated over a time period of 3 months.

Results No significant differences between the treatment group and control group were identified with regard to baseline patient parameters. No clinically significant orthopaedic examination abnormalities, gait abnormalities, biochemical alterations, joint fluid alterations or histopathological alterations were identified over the course of the study.

Conclusion The synthetic lubricin studied herein is both biocompatible and safe for a single administration within the canine stifle joint. Further research is necessary to evaluate the clinical efficacy of the synthetic lubricin in canine osteoarthritic joints.

Keywords

osteoarthritis - biocompatibility - dogs - stifle

Authors' Contributions

K.H. designed, directed and performed the project. A.B. performed the experiment and organized the data. D.L. organized the data and wrote the manuscript. B.G.C. conducted histopathological analysis. E.B. performed the experiment and organized the data. U.K. and S.Y.K. designed the experimental model and analysed the data. H.R. conceived the original idea, devised the project and planned the experiments. D.P. conducted sample preparation, worked out the technical details and contributed to the interpretation of the results.


Supplementary Material



Publication History

Received: 10 December 2020

Accepted: 16 August 2021

Article published online:
01 October 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Marshall W, Bockstahler B, Hulse D, Carmichael S. A review of osteoarthritis and obesity: current understanding of the relationship and benefit of obesity treatment and prevention in the dog. Vet Comp Orthop Traumatol 2009; 22 (05) 339-345
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Sanderson RO, Beata C, Flipo RM. et al. Systematic review of the management of canine osteoarthritis. Vet Rec 2009; 164 (14) 418-424
    CrossrefPubMedGoogle Scholar
  • 3 Aragon CL, Hofmeister EH, Budsberg SC. Systematic review of clinical trials of treatments for osteoarthritis in dogs. J Am Vet Med Assoc 2007; 230 (04) 514-521
    CrossrefPubMedGoogle Scholar
  • 4 DiVincenzo MJ, Frydman GH, Kowaleski MP. et al. Metallosis in a dog as a long-term complication following total hip arthroplasty. Vet Pathol 2017; 54 (05) 828-831
    CrossrefPubMedGoogle Scholar
  • 5 Liska WD, Israel SK. Morbidity and mortality following total hip replacement in dogs. Vet Comp Orthop Traumatol 2018; 31 (03) 218-221
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Kidd SW, Preston CA, Moore GE. Complications of porous-coated press-fit cementless total hip replacement in dogs. Vet Comp Orthop Traumatol 2016; 29 (05) 402-408
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Bayer K, Matiasovic M, Steger H, Böttcher P. Complications and long-term outcome in 16 canine cementless hybrid hip arthroplasties. Vet Comp Orthop Traumatol 2019; 32 (01) 73-78
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Agnello KA, Cimino Brown D, Aoki K, Franklin S, Hayashi K. Risk factors for loosening of cementless threaded femoral implants in canine total hip arthroplasty. Vet Comp Orthop Traumatol 2015; 28 (01) 48-53
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Eskelinen EV, Liska WD, Hyytiäinen HK, Hielm-Björkman A. Canine total knee replacement performed due to osteoarthritis subsequent to distal femur fracture osteosynthesis: two-year objective outcome. Vet Comp Orthop Traumatol 2012; 25 (05) 427-432
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Off W, Matis U. Excision arthroplasty of the hip joint in dogs and cats. Clinical, radiographic, and gait analysis findings from the Department of Surgery, Veterinary Faculty of the Ludwig-Maximilians-University of Munich, Germany. 1997. Vet Comp Orthop Traumatol 2010; 23 (05) 297-305
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Beever LJ, Kulendra ER, Meeson RL. Short and long-term outcome following surgical stabilization of tarsocrural instability in dogs. Vet Comp Orthop Traumatol 2016; 29 (02) 142-148
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Fahie MA, Ortolano GA, Guercio V. et al. A randomized controlled trial of the efficacy of autologous platelet therapy for the treatment of osteoarthritis in dogs. J Am Vet Med Assoc 2013; 243 (09) 1291-1297
    CrossrefPubMedGoogle Scholar
  • 13 Vilar JM, Manera ME, Santana A. et al. Effect of leukocyte-reduced platelet-rich plasma on osteoarthritis caused by cranial cruciate ligament rupture: a canine gait analysis model. PLoS One 2018; 13 (03) e0194752
    CrossrefPubMedGoogle Scholar
  • 14 Silva RF, Carmona JU, Rezende CM. Intra-articular injections of autologous platelet concentrates in dogs with surgical reparation of cranial cruciate ligament rupture: a pilot study. Vet Comp Orthop Traumatol 2013; 26 (04) 285-290
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Schmidt TA, Gastelum NS, Nguyen QT, Schumacher BL, Sah RL. Boundary lubrication of articular cartilage: role of synovial fluid constituents. Arthritis Rheum 2007; 56 (03) 882-891
    CrossrefPubMedGoogle Scholar
  • 16 Jay GD, Waller KA. The biology of lubricin: near frictionless joint motion. Matrix Biol 2014; 39: 17-24
    CrossrefPubMedGoogle Scholar
  • 17 Abubacker S, Dorosz SG, Ponjevic D, Jay GD, Matyas JR, Schmidt TA. Full-length recombinant human proteoglycan 4 interacts with hyaluronan to provide cartilage boundary lubrication. Ann Biomed Eng 2016; 44 (04) 1128-1137
    CrossrefPubMedGoogle Scholar
  • 18 Jay GD. Characterization of a bovine synovial fluid lubricating factor. I. Chemical, surface activity and lubricating properties. Connect Tissue Res 1992; 28 (1-2): 71-88
    CrossrefPubMedGoogle Scholar
  • 19 Samaroo KJ, Tan M, Putnam D, Bonassar LJ. Binding and lubrication of biomimetic boundary lubricants on articular cartilage. J Orthop Res 2017; 35 (03) 548-557
    CrossrefPubMedGoogle Scholar
  • 20 Elsaid KA, Fleming BC, Oksendahl HL. et al. Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury. Arthritis Rheum 2008; 58 (06) 1707-1715
    CrossrefPubMedGoogle Scholar
  • 21 Young AA, McLennan S, Smith MM. et al. Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis. Arthritis Res Ther 2006; 8 (02) R41
    CrossrefPubMedGoogle Scholar
  • 22 Flannery CR, Zollner R, Corcoran C. et al. Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin. Arthritis Rheum 2009; 60 (03) 840-847
    CrossrefPubMedGoogle Scholar
  • 23 Sun Z, Feeney E, Guan Y. et al. Boundary mode lubrication of articular cartilage with a biomimetic diblock copolymer. Proc Natl Acad Sci U S A 2019; 116 (25) 12437-12441
    CrossrefPubMedGoogle Scholar
  • 24 Nemirov D, Nakagawa Y, Sun Z. et al. Effect of lubricin mimetics on the inhibition of osteoarthritis in a rat anterior cruciate ligament transection model. Am J Sports Med 2020; 48 (03) 624-634
    CrossrefPubMedGoogle Scholar
  • 25 Cui Z, Xu C, Li X, Song J, Yu B. Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats. Bone 2015; 74: 37-47
    CrossrefPubMedGoogle Scholar
  • 26 Jay GD, Elsaid KA, Kelly KA. et al. Prevention of cartilage degeneration and gait asymmetry by lubricin tribosupplementation in the rat following anterior cruciate ligament transection. Arthritis Rheum 2012; 64 (04) 1162-1171
    CrossrefPubMedGoogle Scholar
  • 27 Jay GD, Fleming BC, Watkins BA. et al. Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection. Arthritis Rheum 2010; 62 (08) 2382-2391
    CrossrefPubMedGoogle Scholar
  • 28 Teeple E, Elsaid KA, Fleming BC. et al. Coefficients of friction, lubricin, and cartilage damage in the anterior cruciate ligament-deficient guinea pig knee. J Orthop Res 2008; 26 (02) 231-237
    CrossrefPubMedGoogle Scholar
  • 29 Teeple E, Elsaid KA, Jay GD. et al. Effects of supplemental intra-articular lubricin and hyaluronic acid on the progression of posttraumatic arthritis in the anterior cruciate ligament-deficient rat knee. Am J Sports Med 2011; 39 (01) 164-172
    CrossrefPubMedGoogle Scholar
  • 30 Elsaid KA, Zhang L, Waller K. et al. The impact of forced joint exercise on lubricin biosynthesis from articular cartilage following ACL transection and intra-articular lubricin's effect in exercised joints following ACL transection. Osteoarthritis Cartilage 2012; 20 (08) 940-948
    CrossrefPubMedGoogle Scholar
  • 31 Lascelles BD, Roe SC, Smith E. et al. Evaluation of a pressure walkway system for measurement of vertical limb forces in clinically normal dogs. Am J Vet Res 2006; 67 (02) 277-282
    CrossrefPubMedGoogle Scholar
  • 32 Baltzer WI, Smith-Ostrin S, Warnock JJ, Ruaux CG. Evaluation of the clinical effects of diet and physical rehabilitation in dogs following tibial plateau leveling osteotomy. J Am Vet Med Assoc 2018; 252 (06) 686-700
    CrossrefPubMedGoogle Scholar
  • 33 Venator KP, Frye CW, Gamble LJ, Wakshlag JJ. Assessment of a single intra-articular stifle injection of pure platelet rich plasma on symmetry indices in dogs with unilateral or bilateral stifle osteoarthritis from long-term medically managed cranial cruciate ligament disease. Vet Med (Auckl) 2020; 11: 31-38
    PubMedGoogle Scholar
  • 34 Gleghorn JP, Jones ARC, Flannery CR, Bonassar LJ. Boundary mode lubrication of articular cartilage by recombinant human lubricin. J Orthop Res 2009; 27 (06) 771-777
    CrossrefPubMedGoogle Scholar
  • 35 Bhandari M, Bannuru RR, Babins EM. et al. Intra-articular hyaluronic acid in the treatment of knee osteoarthritis: a Canadian evidence-based perspective. Ther Adv Musculoskelet Dis 2017; 9 (09) 231-246
    CrossrefPubMedGoogle Scholar
  • 36 Kawano T, Miura H, Mawatari T. et al. Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental osteoarthritis. Arthritis Rheum 2003; 48 (07) 1923-1929
    CrossrefPubMedGoogle Scholar
  • 37 Smith Jr GN, Myers SL, Brandt KD, Mickler EA. Effect of intraarticular hyaluronan injection in experimental canine osteoarthritis. Arthritis Rheum 1998; 41 (06) 976-985
    CrossrefPubMedGoogle Scholar
  • 38 Jay GD, Haberstroh K, Cha CJ. Comparison of the boundary-lubricating ability of bovine synovial fluid, lubricin, and Healon. J Biomed Mater Res 1998; 40 (03) 414-418
    CrossrefPubMedGoogle Scholar
  • 39 Waller KA, Zhang LX, Elsaid KA, Fleming BC, Warman ML, Jay GD. Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis. Proc Natl Acad Sci U S A 2013; 110 (15) 5852-5857
    CrossrefPubMedGoogle Scholar