TABLE 1.

Mechanism of exercise in the treatment of Osteoarthritis (OA).

Researchers	Model	Exercise types	Related gene/cytokines/protein	Involved in pathways	Improved organization	Functions	Change
He et al., 2020	OA mice model	Cell stretch	Irisin	Erk	Articular cartilage	Apoptosis	↓
Griffin et al., 2020	OA mice model	Wheel-running exercise	—	—	Subchondral bone	Inflammation	↓
Lu et al., 2021	OA rat model	Treadmill exercise	Maresin-1, MMP-13	PI3K/AKT, NF-κB	Synovial	Inflammation	↓
Griffin et al., 2012	OA mice model	Wheel-running exercise	KC, leptin, IL-1Ra	—	Subchondral bone, Articular cartilage	Inflammation	↓
Cormier et al., 2017	OA rat model	Prior wheel running	—	—	Subchondral bone, Articular cartilage	Inflammation	↓
Chen et al., 2020	OA rat model	Treadmill and wheel exercise	IL-1b, IL-6, TNF-a	JNK/NF-kB	Articular cartilage, synovial	Inflammation	↓
Rios et al., 2019	OA rat model	Aerobic exercise	IL-6, TNF-α	—	Subchondral bone	Inflammation	↓
Li K. et al., 2021	OA mice model	Wheel-running exercise	TLR4, MMP-13	—	Articular cartilage	Degradation of ECM	↓
Yang et al., 2020	OA rat model	Treadmill exercise	TRAIL	TRAIL/NF-κB/NLRP3	Articular cartilage	Apoptosis, Inflammation	↓
Allen et al., 2017	OA rat model	Treadmill exercise	—	—	Subchondral bone	Inflammation	↓
Zhang X. et al., 2019	OA rat model	Treadmill exercise	Lc3B, SQSTM1	—	Articular cartilage	Autophagy	↑
Zhang H. et al., 2019	OA rat model	Treadmill exercise	HDAC3	HDAC3/NF-KappaB	Articular cartilage	Inflammation	↓
Galois et al., 2004	OA rat model	Running training	Hsp70	—	Articular cartilage	Apoptosis	↓
Oka et al., 2019	OA mice model	Treadmill exercise	IL-1β, MMP-13	—	Articular cartilage	Inflammation, Degradation of ECM	↓
Blazek et al., 2016	OA rat model	Treadmill exercise	MMP-13,Type II collagen	—	Articular cartilage	Degradation of ECM	↓
Yang et al., 2019	OA rat model	Treadmill exercise	IL - 1β	AMPK/NF – κB	Articular cartilage	Inflammation	↓
Assis et al., 2016	OA rat model	Aerobic exercise	IL-1β, caspase-3, MMP-13	—	Articular cartilage	Inflammation	↓
Baur et al., 2011	OA mice model	Running exercise	ROS, SOD2	—	Articular cartilage	Autophagy	↓
Assis et al., 2015	OA rat model	Treadmill exercise	muscle-specific ring- finger protein 1, atrogin-1	—	Articular cartilage	Degradation of ECM	↓
Yamaguchi et al., 2013	OA rat model	Running	C2C, CPII	—	Articular cartilage	Degradation of ECM	↓
Assis et al., 2018	OA rat model	An aerobic and an aquatic exercise	IL-10, TGF-β, collagen I and II	—	Articular cartilage	Degradation of ECM	↓
Milares et al., 2016	OA rat model	An aquatic exercise	IL1-β, caspase-3	—	Articular cartilage	Inflammation	↓
Szychlinska et al., 2019	OA rat model	Physical activity	IL-6	—	Articular cartilage	Inflammation	↓
Qian et al., 2014	OA rat model	Passive motion	Proteoglycans, type II collagen fibers	—	Articular cartilage	Apoptosis	↓
Yang et al., 2017	OA rat model	Treadmill exercise	LXA4	NF-κB	Articular cartilage	Inflammation	↓
Castrogiovanni et al., 2019	OA rat model	Physical Activity	IL-1β, IL-6, TNF-α, MMP-13	—	synovial	Inflammation	↓
Iijima et al., 2016	OA rat model	Treadmill walking	BMP-2, BMP-6	—	Subchondral bone	Cartilage matrix synthesis	↑
Boudenot et al., 2014	OA rat model	Interval training exercise			Subchondral bone	Apoptosis	↓
Iijima et al., 2017	OA rat model	Treadmill exercise	BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5	BMP	Articular cartilage, Subchondral bone	Inflammation, Apoptosis	↓
Oka et al., 2021	OA mice model	Treadmill exercise	Gremlin-1, MMP-13	—	Articular cartilage	Inflammation	↓
Vasilceac et al., 2021	OA rat model	Resistance training	MMP-2	—	Articular cartilage	Degradation of ECM	↓
Hong et al., 2014	OA rat model	Treadmill exercise	IL-6, EPAS-1, MMP-13	—	Articular cartilage	Degradation of ECM, Apoptosis	↓
Na et al., 2014	OA rat model	Treadmill exercise	C9	—	serum	Inflammation	↓
Cifuentes et al., 2010	OA rat model	Impact exercise	ACAN, COL2a1, TIMP3, MMP	—	Articular cartilage	Autophagy	↑
Yang et al., 2018	OA rat model	Treadmill exercise	LXA4	NF-κB	Synovial	Inflammation	↓
Hsieh and Yang, 2018	OA rat model	Swimming exercises	collagen II, MMP13	—	Articular cartilage, Synovial	Degradation of ECM, Apoptosis	↓
Hao et al., 2021	OA rat model	Body weight-supported treadmill training	collagen II, MMP13	—	Articular cartilage, Subchondral bone	Degradation of ECM, Apoptosis	↓
Iijima et al., 2015	OA rat model	Short-term gentle treadmill walking	—	—	subchondral bone	Apoptosis	↓
Al-Hashem et al., 2017	OA rat model	Swim exercise	TBARS, TNFa, SOD	—	Articular cartilage	Inflammation	↓
Martins et al., 2019	OA rat model	Aerobic training	MIA, IL1β, TNF	—	Articular cartilage	Inflammation	↓
Musumeci et al., 2015	OA rat model	Treadmill exercise	lubricin	—	Articular cartilage, Synovial	Cartilage matrix synthesis	↑
Musumeci et al., 2013	OA rat model	Treadmill exercise	caspase-3	—	Articular cartilage	Apoptosis	↓
Tian et al., 2021	OA rat model	Treadmill exercise	15-HETE	PI3k-Akt	Synovial	Inflammation	↓
Fallah Mohammadi et al., 2013	OA rat model	Treadmill exercise	IL – 1β, TNF – α	—	Articular cartilage	Inflammation	↓
Zhang J. et al., 2021	OA rat model	Swimming exercise	caspase-3	—	Articular cartilage	Apoptosis	↓
Li Z. et al., 2021	OA rat model	Treadmill exercise	P2 × 7	IRE1-mTOR-PERK	Articular cartilage	Autophagy	↑
Guan et al., 2011	OA chicken model	mechanical stimulation	HDAC4	—	Articular cartilage	miR-365	↑
Zhou et al., 2021	OA mice model	Treadmill running	—	—	Articular cartilage	lncRNA H19	↑
Liu Q. et al., 2016	OA cell model	mechanical stimulation	TMSB4	—	Articular cartilage	lncRNA-MSR	↑
Liu et al., 2017	OA cell model	mechanical stimulation	TNF-α	—	Articular cartilage	circRNA-MSR	↓
Fang et al., 2021	OA rabbit model	running experiment	PCNA, SOX9, Col II, Aggrecan	—	Articular cartilage	circUNK	↑