Table 1.

Therapeutic reagents targeting ER stress to alleviate degenerative musculoskeletal diseases

Therapeutic reagents	Effects in targeting ER stress	Roles in degenerative musculoskeletal diseases	Level of evidence	References
4-PBA	Assist protein folding	Inhibit ER stress, apoptosis, and cartilage degradation in anterior cruciate ligament transection rat models Inhibit ER stress-mediated osteoclast differentiation in IL-1β-treated BMSCs Protect NP cell from AGEs-induced apoptosis	In vivo In vitro In vitro	[248] [129] [206]
TUDCA	Assist protein folding	Recover cell proliferation, reduce apoptosis and increase expression of type II collagen in OA chondrocyte Alleviate compression-induced apoptosis and necroptosis of NP cells	In vitro In vitro	[249] [250]
Salubrinal	Inhibit eIF2α dephosphorylation Inhibit protein translation	Inhibit ER stress-mediated upregulation of MMP13 Stimulate the osteoblastogenesis of MC3T3 E1 and inhibit the osteoclastogenesis of RAW264.7	In vitro In vitro	[251] [252]
Guanabenz	Inhibit eIF2α dephosphorylation Inhibit protein translation	Stimulate the osteoblastogenesis of MC3T3 E1 and inhibit the osteoclastogenesis of RAW264.7	In vitro	[252]
CBZ	Increase autophagy	Reduce ER stress, improve hypertrophic chondrocyte differentiation, accelerate bone growth rate, and decrease skeletal dysplasia in metaphyseal chondrodysplasia type Schmid mouse model	In vivo	[253]

ER endoplasmic reticulum, 4-PBA 4-phenylbutiric acid, BMSCs bone marrow mesenchymal stem cells, NP nucleus pulposus, AGEs advanced glycation end products, TUDCA tauroursodeoxycholic acid, OA osteoarthritis, eIF2α α-subunit of eukaryotic translation initiation factor 2, MMP13 matrix metallopeptidase-13, CBZ carbamazepin