Time-Dependent Effects on Synovial Fluid Composition During the Acute Phase of Human Intra-articular Ankle Fracture

Abstract

Background:

The study objective was to examine the effect of time and fracture severity on the undiluted synovial fluid (SF) microenvironment during the acute phase following intra-articular fracture (IAF) of the human ankle.

Methods:

Ankle SF from 54 patients with an acute IAF was analyzed for concentrations of 10 cytokines, 5 matrix metalloproteinases, 2 products of cartilage catabolism, and combined products of heme metabolism. All analytes were correlated with time from fracture and further analyzed for an effect of 3 time subgroups (0-2 days, 3-9 days, and ≥10 days) corresponding to timepoints for clinical ankle fracture interventions. The effect of fracture severity was determined by grouping SF according to the number of radiographic intra-articular fracture lines.

Results:

Fifteen of 18 analytes were significantly correlated with time. Temporal grouping of SF revealed an initial (0-2 days) spike of pro-inflammatory (IL-12p70, IL-1β, IL-6) and anti-inflammatory (IL-10 and IL-4) cytokines, matrix metalloproteinases (MMP) MMP-9, and sGAG, followed immediately (3-9 days) by products of heme metabolism and an unchallenged surge in mediators and products of cartilage catabolism (MMP-1, MMP-2, MMP-3, MMP-10, and CTX-II). After 10 days, there was a decrease in pro- and anti-inflammatory cytokines but a persistence of mediators of ECM catabolism. There was no clear relationship between the number of fracture lines and SF levels of analytes.

Conclusions:

This study demonstrated acute temporal fluctuations following ankle IAF resulting in an overall catabolic environment by 10 days post-fracture and supports consideration of an early evacuation of the joint space to reduce the intra-articular inflammatory burden.

Clinical Relavence:

This study contributes to the understanding of the intra-articular events that potentially contribute to the development of posttraumatic osteoarthritis acutely following IAF in the ankle.

Keywords

ankle fracture synovial fluid posttraumatic osteoarthritis inflammation cytokines matrix metalloproteinases cartilage damage MMPs IL-1

Get full access to this article

View all access options for this article.

References

Adams

Leimer

Setton

et al . Inflammatory microenvironment persists after bone healing in intra-articular ankle fractures. Foot Ankle Int. 2017;38(5):479-484.

Adams

Setton

Bell

et al . Inflammatory cytokines and matrix metalloproteinases in the synovial fluid after intra-articular ankle fracture. Foot Ankle Int. 2015;36(11):1264-1271.

Adams

Jr Nettles

Jones

et al . Inflammatory cytokines and cellular metabolites as synovial fluid biomarkers of posttraumatic ankle arthritis. Foot Ankle Int. 2014;35(12):1241-1249.

Anderson

Chubinskaya

Guilak

et al . Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res. 2011;29(6):802-809.

Anderson

Kilburg

Thomas

Marsh

JL.

Expedited CT-based methods for evaluating fracture severity to assess risk of post-traumatic osteoarthritis after articular fractures. Iowa Orthop J. 2016;36:46-52.

Anderson

Marsh

Brown

TD.

The pathomechanical etiology of post-traumatic osteoarthritis following intraarticular fractures. Iowa Orthop J. 2011;31:1-20.

Behrendt

Preusse-Prange

Kluter

et al . IL-10 reduces apoptosis and extracellular matrix degradation after injurious compression of mature articular cartilage. Osteoarthritis Cartilage. 2016;24(11):1981-1988.

Bigoni

Sacerdote

Turati

et al . Acute and late changes in intraarticular cytokine levels following anterior cruciate ligament injury. J Orthop Res. 2013;31(2):315-321.

Brown

Johnston

Saltzman

Marsh

Buckwalter

JA.

Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20(10):739-744.

10.

Buckwalter

Brown

TD.

Joint injury, repair, and remodeling: roles in post-traumatic osteoarthritis. Clin Orthop Relat Res. 2004;423:7-16.

11.

Catterall

Stabler

Flannery

Kraus

VB.

Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254). Arthritis Res Ther. 2010;12(6):R229.

12.

Daheshia

Yao

JQ.

The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J Rheumatol. 2008;35(12):2306-2312.

13.

Delco

Kennedy

Bonassar

Fortier

LA.

Post-traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches. J Orthop Res. 2017;35(3):440-453.

14.

Dirschl

Marsh

Buckwalter

et al . Articular fractures. J Am Acad Orthop Surg. 2004;12(6):416-423.

15.

Fernandes

Martel-Pelletier

Pelletier

JP.

The role of cytokines in osteoarthritis pathophysiology. Biorheology. 2002;39(1-2):237-246.

16.

Furman

Kimmerling

Zura

et al . Articular ankle fracture results in increased synovitis, synovial macrophage infiltration, and synovial fluid concentrations of inflammatory cytokines and chemokines. Arthritis Rheumatol. 2015;67(5):1234-1239.

17.

Furman

Mangiapani

Zeitler

et al . 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;16(3):R134.

18.

Hooiveld

Roosendaal

van den Berg

Bijlsma

Lafeber

FP.

Haemoglobin-derived iron-dependent hydroxyl radical formation in blood-induced joint damage: an in vitro study. Rheumatology. 2003;42(6):784-790.

19.

Hooiveld

Roosendaal

Wenting

et al . Short-term exposure of cartilage to blood results in chondrocyte apoptosis. Am J Pathol. 2003;162(3):943-951.

20.

Irie

Uchiyama

Iwaso

Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee. Knee. 2003;10(1):93-96.

21.

Jansen

Roosendaal

Hooiveld

et al . Interleukin-10 protects against blood-induced joint damage. Br J Haematol. 2008;142(6):953-961.

22.

Kramer

Hendricks

Wang

Pathogenetic mechanisms of posttraumatic osteoarthritis: opportunities for early intervention. Int J Clin Exp Med. 2011;4(4):285-298.

23.

Kyostio-Moore

Nambiar

Hutto

et al . STR/ort mice, a model for spontaneous osteoarthritis, exhibit elevated levels of both local and systemic inflammatory markers. Comp Med. 2011;61(4):346-355.

24.

Larsson

Englund

Struglics

Lohmander

LS.

Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy. Osteoarthritis Cartilage. 2015;23(11):1906-1914.

25.

Lawrence

Birmingham

Toth

AP.

Emerging ideas: prevention of posttraumatic arthritis through interleukin-1 and tumor necrosis factor-alpha inhibition. Clin Orthop Rel Res. 2011;469(12):3522-3526.

26.

Leimer

Pappan

Nettles

et al . Lipid profile of human synovial fluid following intra-articular ankle fracture. J Orthop Res. 2016;35:657-666.

27.

Lewis

Hembree

Furman

et al . Acute joint pathology and synovial inflammation is associated with increased intra-articular fracture severity in the mouse knee. Osteoarthritis Cartilage. 2011;19(7):864-873.

28.

Lewis

Jr Furman

Zeitler

et al . Genetic and cellular evidence of decreased inflammation associated with reduced incidence of posttraumatic arthritis in MRL/MpJ mice. Arthritis Rheum. 2013;65(3):660-670.

29.

Louer

Furman

Huebner

et al . Diet-induced obesity significantly increases the severity of posttraumatic arthritis in mice. Arthritis Rheum. 2012;64(10):3220-3230.

30.

Yan

Zheng

et al . Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells. F1000Research. 2015;4.

31.

Marsh

Buckwalter

Gelberman

et al . Articular fractures: does an anatomic reduction really change the result? J Bone Joint Surg Am. 2002;84-a(7):1259-1271.

32.

Olson

Furman

Kraus

Huebner

Guilak

Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture. J Orthop Res. 2015;33(9):1266-1277.

33.

Ostalowska

Kasperczyk

et al . Oxidant and anti-oxidant systems of synovial fluid from patients with knee post-traumatic arthritis. J Orthop Res. 2007;25(6):804-812.

34.

Parratte

Boyer

Piriou

et al . Total knee replacement following intra-articular malunion. Orthop Traumatol Surg Res. 2011;97(6 suppl):S118-S123.

35.

Scott

Midha

Rashid

et al . Correlation of gene and mediator expression with clinical endpoints in an acute interleukin-1beta-driven model of joint pathology. Osteoarthritis Cartilage. 2009;17(6):790-797.

36.

Stolberg-Stolberg

Furman

Garrigues

et al . Effects of cartilage impact with and without fracture on chondrocyte viability and the release of inflammatory markers. J Orthop Res. 2013;31(8):1283-1292.

37.

Tickner

Gutteridge

JM.

A simple colorimetric method for the estimation of plasma biliverdin. Clin Chim Acta. 1978;85(2):125-129.

38.

van Meegeren

Roosendaal

Jansen

Lafeber

Mastbergen

SC.

Blood-induced joint damage: the devastating effects of acute joint bleeds versus micro-bleeds. Cartilage. 2013;4(4):313-320.

39.

van Meegeren

Roosendaal

van Veghel

Mastbergen

Lafeber

FP.

A short time window to profit from protection of blood-induced cartilage damage by IL-4 plus IL-10. Rheumatology. 2013;52(9):1563-1571.

40.

van Vulpen

van Meegeren

Roosendaal

et al . Biochemical markers of joint tissue damage increase shortly after a joint bleed; an explorative human and canine in vivo study. Osteoarthritis Cartilage. 2015;23(1):63-69.

41.

Wojdasiewicz

Poniatowski

Szukiewicz

The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators of Inflammation. 2014;2014:561459.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.21 MB