The Role of Macrophages in Osteoarthritis and Cartilage Repair

Overview

Journal Osteoarthritis Cartilage

Specialties Orthopedics
Rheumatology

Date 2020 Jan 12

PMID 31926267

Citations 114

Authors

C-L Wu

N S Harasymowicz

M A Klimak

K H Collins

F Guilak

Affiliations

Soon will be listed here.

Abstract

Osteoarthritis (OA) is a family of degenerative diseases affecting multiple joint tissues. Despite the diverse etiology and pathogenesis of OA, increasing evidence suggests that macrophages can play a significant role in modulating joint inflammation, and thus OA severity, via various secreted mediators. Recent advances in next-generation sequencing technologies coupled with proteomic and epigenetic tools have greatly facilitated research to elucidate the embryonic origin of macrophages in various tissues including joint synovium. Furthermore, scientists have now begun to appreciate that macrophage polarization can span beyond the conventionally recognized binary states (i.e., pro-inflammatory M1-like vs anti-inflammatory M2-like) and may encompass a broad spectrum of phenotypes. Although the presence of these cells has been shown in multiple joint tissues, additional mechanistic studies are required to provide a comprehensive understanding of the precise role of these diverse macrophage populations in OA onset and progression. New approaches that can modulate macrophages into desired functional phenotypes may provide novel therapeutic strategies for preventing OA or enhancing cartilage repair and regeneration.

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References

Batoon L, Millard S, Wullschleger M, Preda C, Wu A, Kaur S . CD169 macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair. Biomaterials. 2017; 196:51-66. DOI: 10.1016/j.biomaterials.2017.10.033. View

Chuckpaiwong B, Charles H, Kraus V, Guilak F, Nunley J . Age-associated increases in the size of the infrapatellar fat pad in knee osteoarthritis as measured by 3T MRI. J Orthop Res. 2010; 28(9):1149-54. PMC: 3625521. DOI: 10.1002/jor.21125. View

Blom A, van Lent P, Libregts S, Holthuysen A, van der Kraan P, van Rooijen N . Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3. Arthritis Rheum. 2006; 56(1):147-57. DOI: 10.1002/art.22337. View

Udalova I, Mantovani A, Feldmann M . Macrophage heterogeneity in the context of rheumatoid arthritis. Nat Rev Rheumatol. 2016; 12(8):472-85. DOI: 10.1038/nrrheum.2016.91. View

Sakurai Y, Fujita M, Kawasaki S, Sanaki T, Yoshioka T, Higashino K . Contribution of synovial macrophages to rat advanced osteoarthritis pain resistant to cyclooxygenase inhibitors. Pain. 2018; 160(4):895-907. DOI: 10.1097/j.pain.0000000000001466. View

Davies L, Rosas M, Smith P, Fraser D, Jones S, Taylor P . A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation. Eur J Immunol. 2011; 41(8):2155-64. DOI: 10.1002/eji.201141817. View

Ginhoux F, Guilliams M . Tissue-Resident Macrophage Ontogeny and Homeostasis. Immunity. 2016; 44(3):439-449. DOI: 10.1016/j.immuni.2016.02.024. View

Klein-Wieringa I, Kloppenburg M, Bastiaansen-Jenniskens Y, Yusuf E, Kwekkeboom J, El-Bannoudi H . The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype. Ann Rheum Dis. 2011; 70(5):851-7. DOI: 10.1136/ard.2010.140046. View

Tu J, Hong W, Guo Y, Zhang P, Fang Y, Wang X . Ontogeny of Synovial Macrophages and the Roles of Synovial Macrophages From Different Origins in Arthritis. Front Immunol. 2019; 10:1146. PMC: 6558408. DOI: 10.3389/fimmu.2019.01146. View

10.

Sheng J, Ruedl C, Karjalainen K . Most Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells. Immunity. 2015; 43(2):382-93. DOI: 10.1016/j.immuni.2015.07.016. View

11.

Bondeson J, Blom A, Wainwright S, Hughes C, Caterson B, van den Berg W . The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis Rheum. 2010; 62(3):647-57. DOI: 10.1002/art.27290. View

12.

Gomez-Aristizabal A, Gandhi R, Mahomed N, Marshall K, Viswanathan S . Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study. Arthritis Res Ther. 2019; 21(1):26. PMC: 6339358. DOI: 10.1186/s13075-018-1798-2. View

13.

Kaur S, Raggatt L, Batoon L, Hume D, Levesque J, Pettit A . Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches. Semin Cell Dev Biol. 2016; 61:12-21. DOI: 10.1016/j.semcdb.2016.08.009. View

14.

Bertrand J, Jalil A, Klaine M, Jung S, Cumano A, Godin I . Three pathways to mature macrophages in the early mouse yolk sac. Blood. 2005; 106(9):3004-11. DOI: 10.1182/blood-2005-02-0461. View

15.

Tang R, Harasymowicz N, Wu C, Collins K, Choi Y, Oswald S . Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet-induced obesity. Sci Adv. 2020; 6(19):eaaz7492. PMC: 7209997. DOI: 10.1126/sciadv.aaz7492. View

16.

Misharin A, Cuda C, Saber R, Turner J, Gierut A, Haines 3rd G . Nonclassical Ly6C(-) monocytes drive the development of inflammatory arthritis in mice. Cell Rep. 2014; 9(2):591-604. PMC: 4223808. DOI: 10.1016/j.celrep.2014.09.032. View

17.

Blomgran P, Blomgran R, Ernerudh J, Aspenberg P . A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat. Sci Rep. 2016; 6:29824. PMC: 4942825. DOI: 10.1038/srep29824. View

18.

Sun A, Panchal S, Friis T, Sekar S, Crawford R, Brown L . Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis. PLoS One. 2017; 12(8):e0183693. PMC: 5578643. DOI: 10.1371/journal.pone.0183693. View

19.

Murata M, Yudoh K, Masuko K . The potential role of vascular endothelial growth factor (VEGF) in cartilage: how the angiogenic factor could be involved in the pathogenesis of osteoarthritis?. Osteoarthritis Cartilage. 2007; 16(3):279-86. DOI: 10.1016/j.joca.2007.09.003. View

20.

Misra D, Fielding R, Felson D, Niu J, Brown C, Nevitt M . Risk of Knee Osteoarthritis With Obesity, Sarcopenic Obesity, and Sarcopenia. Arthritis Rheumatol. 2018; 71(2):232-237. PMC: 6374038. DOI: 10.1002/art.40692. View