Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients

Wood, Matthew J.; Leckenby, Adam; Reynolds, Gary; Spiering, Rachel; Pratt, Arthur G.; Rankin, Kenneth; Isaacs, John D.; Haniffa, Muzlifah; Milling, Simon; Hilkens, Catharien M. U.

doi:10.1172/jci.insight.125325

Cited by 85 publications

(93 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Macrophages are innate immune cells that express MHC class II, which gives them the ability to initiate adaptive immune response through T cell activation. Macrophage from synovial tissue expresses CD14, CD68, CSF1R, HLA-DRA, and MARCO (35).…”

Section: Macrophagesmentioning

confidence: 99%

“…Although some positive effect was seen in diminishing the pain, MRI images showed no change in synovitis after anti-GM-CSF treatment (50). Wood et al (35) declared that sub-groups of synovial macrophages functions as a spectrum with different remodeling signatures and Tardito et al (51) emphasized the need of a not classical sub-division into M1 and M2 macrophages, but a M1 and M2 coexistence and equilibrium.…”

Section: Macrophages In Oamentioning

confidence: 99%

See 1 more Smart Citation

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

View full text Add to dashboard Cite

Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

show abstract

Section: Macrophagesmentioning

confidence: 99%

Section: Macrophages In Oamentioning

confidence: 99%

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, we did observe that a subset of the OA patient exhibited a transcriptional signature of inflammation comparable to RA. This observation was shown independently by another group that classified two subtypes of macrophages in OA (55). Furthermore, AMP characterized myeloid subpopulations from joint replacements and compared the transcriptional profile of macrophages from OA and RA patients (43).…”

Section: Discussionmentioning

confidence: 60%

Macrophages drive the inflammatory phase in experimental osteoarthritis

Montgomery¹,

Fahy

Hamilton

et al. 2020

Preprint

View full text Add to dashboard Cite

Macrophages fulfill critical functions in maintaining tissue homeostasis in steady-state, as well as in inflammation and immune response. Inflammation is not considered a major driver of osteoarthritis (OA), but macrophages have been implicated in its pathogenesis. Here, we use two mouse models of experiment OA -collagenase-induced osteoarthritis (CIOA) and destabilization of the medial meniscus (DMM) -to quantify the immune cell infiltration into the knee joint during the early stages of disease. We find that the peak of inflammation occurs at day 3 in CIOA and is characterized by a transitory increase in neutrophils and monocytes and a longer-lived expansion of synovial macrophages. Macrophage sub-populations are disproportionally expanded with CX3CR1+ cells accounting for a larger proportion of the macrophage compartment. Transcriptional profiling demonstrates that synovial macrophages up-regulate inflammatory genes coinciding with peak inflammation and down-regulate genes associated with homeostasis and tissue-residence. Female mice exhibit a similar expansion of macrophages post-CIOA indicating that the inflammatory phase is not sex-specific. Finally, we find day 7 post-DMM is also characterized by increases in neutrophil, monocyte, and macrophage sub-population numbers. These results support a role for macrophages in early stages of OA through driving the inflammatory phase. Further investigation may elucidate potential targets for the prevention or attenuation of OA-associated cartilage damage.

show abstract

“…Within the increased macrophage population we further investigated whether loading induced differences in M1 and M2 extreme polarized macrophages phenotypes (13). Previously, a mixture of both M1-and M2-related genes was expressed by synovial macrophages across OA patients (12). Interestingly, both the number of M1 (CD197+) and M2 (Egr2+) macrophage subsets increased significantly with tibial loading in the inguinal lymph node of adult female mice (Figure 2A).…”

Section: Macrophage Population Increased With Cyclic Tibial Compressimentioning

confidence: 86%

“…Macrophages are associated with inflammation in OA (12). Using 10-and 26-week-old C57Bl/6 female mice, we examined whether the macrophage cell population changed with cyclic tibial compression of the left tibia (9.0N peak, 1200 cycles, 4Hz frequency, 5 days/week).…”

Section: Macrophage Population Increased With Cyclic Tibial Compressimentioning

confidence: 99%

T cells Mediate Progression of Load-Induced Osteoarthritis

Wheeler

Antoinette

Kim

et al. 2020

Preprint

View full text Add to dashboard Cite

Osteoarthritis (OA) is a degenerative disease that manifests as joint damage and synovial inflammation. To date, most studies have focused on the decrease in cartilage stiffness, chondrocyte viability, and changes in matrix-degrading enzymes. With the exception of a few inflammatory cytokines and macrophages, the immune response in OA is poorly characterized, and the crosstalk of joint damage with T and B cells in local lymph nodes is unknown. Here, using an in vivo mouse model of mechanical loading of mouse tibia, we demonstrate that CD8+ T cells and subsets of CD4+ T cells, and not B cells, increase in the local lymph nodes and contribute to the progression of load-induced OA pathology. We demonstrate that T cell response is sex-and age-dependent. Mechanical loading of T cell knock-out mice that lack αβ T cell receptor carrying cells resulted in attenuation of both cartilage degradation and osteophyte formation in loaded joints, with a concomitant increase in γδ+ T cells. Restricting the migration of T cells in lymphoid tissues through the systemic treatment using Sphingosine-1-phosphate (S1P) inhibitor, decreased localization of T cells in synovium, and attenuated cartilage degradation. Our results lay the foundation of the role T cells play in the joint damage of load-induced OA and allude to the use of S1P inhibitors and T cell immunotherapies for slowing the progression of OA pathology.

show abstract

Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients

Cited by 85 publications

References 45 publications

Macrophage: A Potential Target on Cartilage Regeneration

Macrophage: A Potential Target on Cartilage Regeneration

Macrophages drive the inflammatory phase in experimental osteoarthritis

T cells Mediate Progression of Load-Induced Osteoarthritis

Contact Info

Product

Resources

About