TABLE 2.
The roles of exerkines (cardiokines and adipokines) in OA.
| Exerkines | Origin | Effects in tissue | Immunomodulatory properties | Signaling pathway | Reference |
|---|---|---|---|---|---|
| GDF-15 | cardiokine | chondrocyte | Negative correlation: cellular senescence | MAPK14 | Bennell et al. (2022) |
| Activin A | cardiokine | chondrocyte, FLSs | Positive correlation: anabolic factor in cartilage | mIL-6R, sIL-6R, IL-6 trans-signaling | Silacci et al. (1998), Dagostino et al. (2005), Pedersen and Febbraio (2008b), Andersson et al. (2010), Haugen et al. (2010), Suzuki et al. (2010), Rose-John (2012), Tsuchida et al. (2012), Hunter and Jones (2015), Nasi et al. (2016), Yang et al. (2017), Wiegertjes et al. (2020) |
| Negative correlation: correlate with inflammatory cytokines | |||||
| FSTL1 | Cardiokine | Chondrocyte, FLSs | Negative correlation: along the interface of eroding bone and inflammatory synovial pannus; pro-inflammatory in OA; FLSs proliferation; promote chondrocytes apoptosis | NF-κB pathway, SAPK/JNK/Caspase3 | Calandra and Roger (2003), Liu and Hu (2012), Moon et al. (2013), Chaly et al. (2015), Ni et al. (2015), Chang et al., (2019), Hu et al. (2019), Li et al. (2020), Xu et al. (2020) |
| MIF | Cardiokine | FLSs | Negative correlation: correlate with the severity of OA and related pain | N/A | Talabot-Ayer et al. (2012), Li et al. (2017), He et al. (2020b) |
| Interleukin-33 | Cardiokine | Chondrocyte | Negative correlation: increase inflammation and cartilage degradation | N/A | Loughlin (2005), Thysen et al. (2015), Kim et al. (2017), Lee et al. (2019) |
| Secreted frizzled-related protein | Cardiokine | Chondrocyte, mesenchymal stem cells | Positive correlation: regulate chondrocyte differentiation and survival; modulate joint homeostasis; delaying the maturation of proliferative chondrocytes into hypertrophic chondrocytes | polymorphism in SFRP cis-acting regulatory elements, | Bouassida et al. (2010), Neumann et al. (2016), Macdonald et al. (2019), Martinez-Huenchullan et al. (2020), Yuan et al. (2023) |
| Neuregulin | Cardiokine | Chondrocyte | Positive correlation: inhibiting the inflammation, protecting against apoptosis of chondrocyte, and decreasing the degradation of extracellular matrix | MAPK, JNK | Challa et al. (2010) |
| Adiponectin | Adipokines | Chondrocyte | Positive correlation: increase proliferation of chondrocytes and the type II collagen and aggrecan; alleviates the calcification of OA chondrocytes; matrix remodelling | AMPK, mTOR | Chen et al. (2010), Seo et al. (2011), Cheleschi et al. (2018), Franco-Trepat et al. (2019b), Cheleschi et al. (2019), Law et al. (2020), Chang et al. (2021) |
| Visfatin | Adipokines | Chondrocyte, FLSs | Negative correlation: enhances intercellular adhesion molecule type 1 expression; facilitates the adhesion of monocytes; induce apoptosis and oxidative stress; enhanced VEGF expression and facilitates angiogenesis; damages the microtubule and microfilament networks | GSK3β, ICAM-1, VEGF | Hu et al. (2010), Hehir and Morrison (2012), Yang et al. (2019), Barbalho et al. (2020), Chang et al. (2020), Yang et al. (2020), Luo et al. (2021), Bolander et al. (2023) |
| Apelin | adipokines | chondrocyte, FLSs | Negative correlation: exacerbated osteoarthritis pathogenesis; promoted chondrocyte proliferation and induced expression of MMPs and IL-1β | PI3K, ERK | Hu et al. (2010), Hu et al. (2011), Chang et al. (2020), Luo et al. (2021) |