Table 1 Characteristics and major conclusion of included studies

Mahon et al. [29]

PBMC

Human

In vitro

BCP promotes macrophage M1 polarization during OA pathogenesis

2DG reverses BCP-induced M1 polarization in OA

Zhou et al. [30]

RAW264.7

Mouse

In vitro & In vivo

ACLT model induces an increase of M1 polarization in synovial macrophage.

Kin attenuates the number of M1 macrophage and up-regulated the M2 macrophage.

Jablonski et al. [31]

N/A

Mouse

In vivo

The predominant macrophage population observed in uninjured knee joint is M1 macrophage.

Benjamin et al. [32]

N/A

Dog

In vivo

CR (cruciate rupture) model leads to a M1 polarization in synovial macrophage.

Haltmayer et al. [33]

N/A

Horse

In vitro

The osteochondral-synovial explant co-culture OA-model indicates a shift towards M1 phenotype during OA progression

Liu et al. [34]

Synovial fluid; PBMC

Human

In vivo

Human knee synovial macrophage displays an increased M1 polarization and decreased M2 polarization.

Sambamurthy et al. [35]

N/A

Mouse

In vivo

DMM model presents an elevated M1 polarization and decreased M2 polarization during OA progression

Wang et al. [36]

BMMC

Mouse

In vivo & In vitro

DMM model demonstrates increased numbers of M1 macrophages and decreased number of M2 macrophage. BTZ could reversed this pathological process

Zhang et al. [37]

Synovium

Mouse

In vivo

Both human OA and CIOA model display an elevated M1 polarization

Timur et al. [38]

Hoffa’s fat pad

Human

In vivo

PGE2 released by OA HFP is positively associated with M1 macrophages polarization, indicating a role for macrophages. Celecoxib modulated the inflammation ratio towards a more favorable anti-inflammatory M2 phenotype

Topoluk et al. [39]

Synovium and cartilage explant

Human

In vitro

OA coculture of synovium with cartilage demonstrates increased M1 polarization.

Wu et al. [13]

N/A

Mouse

In vivo

DMM model demonstrates increased numbers of M1 macro

Manferdini et al. [40]

Human SMMC & PBMC

Human

In vitro

ASCs are responsible for the switching of activated-M1-like inflammatory macrophages to a M2-like phenotype

Pal et al. [41]

PBMC

Human

In vitro

SFN could shift monocyte/macrophage differentiation towards the anti-inflammatory M2 type

Siebelt et al. [42]

Human monocyte

Rat

In vitro

TA induces a M2 polarization in macrophage

Fahy et al. [43]

SMMC and fibroblast

Human

In vitro

M1 macrophages downregulate MSC chondrogenesis

Tsuneyoshi et al. [44]

N/A

Human

In vitro

The distribution and M1/M2 expression profiles of synovial macrophages are different between OA and RA synovium.

Zhang et al. [45]

N/A

Rat

In vivo

In a Rat osteochondral defect model, M2 macrophages in cartilage and synovium increase. The intervention of exosomes increases the M2 macrophages and decreases M1 macrophage

Hu et al. [46]

N/A

Rat

In vivo

Quercetin promotes cartilage repair by modulating macrophages polarization to M2 macrophages in Rat OA model

Dai et al. [47]

RAW264.7

Rat

In vivo & In vitro

SCII immunomodulates a phenotype shift of macrophages from M0 to M2 during OA progression

Barreto et al. [48]

PBMC

Human

In vitro

Lumican contributes to the innate immune-mediated pathogenesis of primary IOA via macrophage M1 polarization

Kraus et al. [49]

N/A

Human

In vivo

One patient OA synovium presents M1 and M2 marker simultaneously.

Utomo et al. [50]

PBMC

Human

In vitro

Dexamethasone lowers M1/M2 proportion in OA synovium.

Perla et al. [51]

THP-1 cell;

PBMC

Human

In vitro

Overexpression of CD163 contributes the transition from M1 to M2 when stimulated with LPS

Nobuaki et al. [52]

N/A

Mouse

In vivo

Polarization towards M2-like macrophages from M1-like macrophages in the synovium is associated with OA alleviation by SRT2104.

Menarim et al. [53]

BMMC

Horse

In vitro

BMNCs cultured in normal synovial fluid or inflamed synovial fluid exhibit aspects of both M1 and M2 phenotypes and immunoregulatory response.

Zhou et al. [54]

RAW264.7

Mouse

In vivo & In vitro

Modified Nanoparticles suppress M1 macrophages and upregulate M2 macrophage infiltration in the synovium, thus preventing cartilage degeneration

Shu et al. [55]

N/A

Mouse

In vivo

Hyaluronan could increase the anti-fibrotic M2c macrophages (F4/80⁺CD206⁺CD301⁺) 12 weeks post DMM