Effect of Interleukin-10 Overexpression on the Properties of Healing Tendon in a Murine Patellar Tendon Model

Overview

Journal J Hand Surg Am

Publisher Elsevier

Date 2008 Dec 17

PMID 19084188

Citations 24

Authors

Eric T Ricchetti

Sudheer C Reddy

Heather L Ansorge

Miltiadis H Zgonis

Jonathan P Van Kleunen

Kenneth W Liechty

Louis J Soslowsky

Pedro K Beredjiklian

Affiliations

Soon will be listed here.

Abstract

Purpose: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine shown to inhibit scar formation in fetal wound healing. The role of IL-10 in adult tendon healing and scar formation, however, remains unknown. The objective of this study is to investigate the effect of IL-10 overexpression on the properties of adult healing tendon using a well-established murine model of tendon injury and a lentiviral-mediated method of IL-10 overexpression.

Methods: A murine model of patellar tendon injury was used and animals divided into 3 groups. Mice received bilateral patellar tendon injections with a lentiviral vector containing an IL-10 transgene (n = 34) or no transgene (n = 34). Control mice (n = 34) received injections of sterile saline. All animals then were subjected to bilateral, central patellar tendon injuries 2 days after injection and were killed at 5, 10, 21, and 42 days after injury. IL-10 content was analyzed by immunohistochemistry (n = 4/group). Tendon healing was evaluated by histology (n = 4/group) and biomechanical analysis (n = 10/group).

Results: Overexpression of IL-10 in patellar tendon was confirmed after injection of the lentiviral vector. IL-10 immunostaining was increased at day 10 in the IL-10 group relative to that in controls. Histologically, there was no significant difference in angular deviation between groups at day 21, but a trend toward decreased angular deviation in controls relative to that in empty vector group mice was seen at day 42. Biomechanically, the IL-10 group showed significantly increased maximum stress at day 42 relative to that in controls. Percent relaxation showed a trend toward an increase at day 10 and a significant increase at day 42 in the IL-10 group relative to that in controls.

Conclusions: This study demonstrates successful gene transfer of IL-10 into adult murine patellar tendon using a lentiviral vector. Although the effects of overexpression of IL-10 on adult tendon healing have not yet been fully elucidated, the current study may help to further clarify the mechanisms of tendon injury and repair.

Citing Articles

Preclinical assessment of IL-1β primed human umbilical cord mesenchymal stem cells for tendon functional repair through TGF-β/IL-10 signaling.

Wang S, Yao Z, Chen L, Li J, Chen S, Fan C Heliyon. 2023; 9(11):e21411.

PMID: 37954299 PMC: 10638607. DOI: 10.1016/j.heliyon.2023.e21411.

Exosome Cell Origin Affects Markers of Tendon Repair in Ovine Macrophages and Tenocytes.

von Stade D, Meyers M, Johnson J, Schlegel T, Romeo A, Regan D Tissue Eng Part A. 2023; 29(9-10):282-291.

PMID: 36792933 PMC: 10178933. DOI: 10.1089/ten.TEA.2022.0185.

Advanced Gene Therapy Strategies for the Repair of ACL Injuries.

Amini M, Venkatesan J, Liu W, Leroux A, Nguyen T, Madry H Int J Mol Sci. 2022; 23(22).

PMID: 36430947 PMC: 9695211. DOI: 10.3390/ijms232214467.

New frontiers of tendon augmentation technology in tissue engineering and regenerative medicine: a concise literature review.

Makuku R, Werthel J, Zanjani L, Nabian M, Tantuoyir M J Int Med Res. 2022; 50(8):3000605221117212.

PMID: 35983666 PMC: 9393707. DOI: 10.1177/03000605221117212.

Engineering Musculoskeletal Grafts for Multi-Tissue Unit Repair: Lessons From Developmental Biology and Wound Healing.

Zhang X, Wang D, Mak K, Tuan R, Ker D Front Physiol. 2021; 12:691954.

PMID: 34504435 PMC: 8421786. DOI: 10.3389/fphys.2021.691954.

References

DiPietro L, Polverini P, Rahbe S, Kovacs E . Modulation of JE/MCP-1 expression in dermal wound repair. Am J Pathol. 1995; 146(4):868-75. PMC: 1869244. View

Sena-Esteves M, Tebbets J, Steffens S, Crombleholme T, Flake A . Optimized large-scale production of high titer lentivirus vector pseudotypes. J Virol Methods. 2004; 122(2):131-9. DOI: 10.1016/j.jviromet.2004.08.017. View

Beredjiklian P, Favata M, Cartmell J, Flanagan C, Crombleholme T, Soslowsky L . Regenerative versus reparative healing in tendon: a study of biomechanical and histological properties in fetal sheep. Ann Biomed Eng. 2003; 31(10):1143-52. DOI: 10.1114/1.1616931. View

Rowlatt U . Intrauterine wound healing in a 20 week human fetus. Virchows Arch A Pathol Anat Histol. 1979; 381(3):353-61. DOI: 10.1007/BF00432477. View

Crosby C, Wehbe M . Early protected motion after extensor tendon repair. J Hand Surg Am. 1999; 24(5):1061-70. DOI: 10.1053/jhsu.1999.1061. View

Lattermann C, Zelle B, Whalen J, Baltzer A, Robbins P, Niyibizi C . Gene transfer to the tendon-bone insertion site. Knee Surg Sports Traumatol Arthrosc. 2004; 12(5):510-5. DOI: 10.1007/s00167-003-0482-4. View

Slate R, Posnick J, Wells M, Goldstein J, Keeley F, Thorner P . Fetal tibial bone healing in utero: the effects of miniplate fixation. Plast Reconstr Surg. 1993; 92(5):874-83. View

Ip W, Chow S . Results of dynamic splintage following extensor tendon repair. J Hand Surg Br. 1997; 22(2):283-7. DOI: 10.1016/s0266-7681(97)80084-8. View

Gerich T, Kang R, Fu F, Robbins P, Evans C . Gene transfer to the patellar tendon. Knee Surg Sports Traumatol Arthrosc. 1997; 5(2):118-23. DOI: 10.1007/s001670050037. View

10.

Heyborne K, McGregor J, Henry G, Witkin S, Abrams J . Interleukin-10 in amniotic fluid at midtrimester: immune activation and suppression in relation to fetal growth. Am J Obstet Gynecol. 1994; 171(1):55-9. DOI: 10.1016/s0002-9378(94)70077-x. View

11.

Evans R . Clinical application of controlled stress to the healing extensor tendon: a review of 112 cases. Phys Ther. 1989; 69(12):1041-9. DOI: 10.1093/ptj/69.12.1041. View

12.

Cadet P, Rady P, Tyring S, Yandell R, Hughes T . Interleukin-10 messenger ribonucleic acid in human placenta: implications of a role for interleukin-10 in fetal allograft protection. Am J Obstet Gynecol. 1995; 173(1):25-9. DOI: 10.1016/0002-9378(95)90164-7. View

13.

Soslowsky L, Thomopoulos S, Tun S, Flanagan C, Keefer C, Mastaw J . Neer Award 1999. Overuse activity injures the supraspinatus tendon in an animal model: a histologic and biomechanical study. J Shoulder Elbow Surg. 2000; 9(2):79-84. View

14.

Chow J, Thomes L, Dovelle S, Milnor W, Seyfer A, Smith A . A combined regimen of controlled motion following flexor tendon repair in "no man's land". Plast Reconstr Surg. 1987; 79(3):447-55. DOI: 10.1097/00006534-198703000-00025. View

15.

Krummel T, Nelson J, Diegelmann R, Lindblad W, SALZBERG A, Greenfield L . Fetal response to injury in the rabbit. J Pediatr Surg. 1987; 22(7):640-4. DOI: 10.1016/s0022-3468(87)80117-3. View

16.

Moore K, OGarra A, de Waal Malefyt R, Vieira P, Mosmann T . Interleukin-10. Annu Rev Immunol. 1993; 11:165-90. DOI: 10.1146/annurev.iy.11.040193.001121. View

17.

Gelberman R, Botte M, Spiegelman J, Akeson W . The excursion and deformation of repaired flexor tendons treated with protected early motion. J Hand Surg Am. 1986; 11(1):106-10. DOI: 10.1016/s0363-5023(86)80115-0. View

18.

Gerich T, Ghivizani S, Fu F, Robbins P, Evans C . [Gene transfer into the patellar tendon of rabbits: a preliminary study of locoregional expression of growth factors]. Wien Klin Wochenschr. 1997; 109(11):384-9. View

19.

Liechty K, Crombleholme T, Cass D, Martin B, Adzick N . Diminished interleukin-8 (IL-8) production in the fetal wound healing response. J Surg Res. 1998; 77(1):80-4. DOI: 10.1006/jsre.1998.5345. View

20.

Fortunato S, Menon R, Swan K, Lombardi S . Interleukin-10 inhibition of interleukin-6 in human amniochorionic membrane: transcriptional regulation. Am J Obstet Gynecol. 1996; 175(4 Pt 1):1057-65. DOI: 10.1016/s0002-9378(96)80053-6. View