Table 2.

OPN involves bone metabolism in OA and OP.

Reference	disease	Subjects	Test items	Main results
Elmazoglu, et al. (72)	OA	Human OA chondrocyte	BMP	S-allylcysteine exhibits anti-osteoarthritic properties through suppressing the expression of IL-1β, IL-6, OPN and BMP in chondrocytes.
Qian, et al. (71)	OA	Serum and synovial tissue	BMD	Increased serum OPN level in OA and RA is related to the activity of osteoclasts and bone erosion in CIA mice.
Lin, et al. (45)	OA	Subchondral bone and osteoclasts	OCN, Runx2, ALP	OPN promotes osteoclastogenesis in the subchondral bone, regulates OA subchondral bone metabolism and accelerates subchondral bone remodeling.
Cassuto, et al. (53)	OA	OA patients blood samples	BALP, OPG, sclerostin	Total hip arthroplasties patients present the second peak of inflammation five years post-surgery which may stimulate bone remodeling and new synthetic coupling, characterized by increasing bone anabolic transition markers BALP and RANKL/OPG.
Kulsirirat, et al. (73)	OA	Mesenchymal stem cells	Runx2, Sox9, OPN	Andrographolide enhance osteogenesis and chondrogenesis by increasing the expression of osteogenic and chondrogenic differentiation, including Runx2, OPN, Sox9.
Li, et al. (51)	OA	Adipose mesenchymal stem cell	OCN, Runx2	IL-1β treatment inhibits the viability and migration of chondrocytes, enhances cell apoptosis, increase OPN level, decrease the mRNA and protein level of Col1a1, Col2a1, OCN, Runx2. Extracellular vesicles-chitosan oligosaccharide conjugates could reverse the effect of IL-1β on cartilage damage.
Tang, et al. (74)	OP	C57/B6L mice and chondrocytes	Sox9, CyclinD1, PTH1R, Osx, Runx2, ATF4, OCN, OPN	Runx1f/fCol2α1-cre mice exhibits impaired cartilage formation, decreases bone density, accompanied with decreased expression of osteoblast differentiation genes including Osx, Runx2, ATF4 and osteoblast marker genes including OCN and OPN in chondrocytes.
Xiao, et al. (75)	OP	C57BL/6 J mice	Vascular endothelial growth factor (VEGF)	Ovariectomy mice presents osteoporosis of the vertebra and osteochondral remodeling of the endplate with increased endplate porosity and decreased disc volume.
Li, et al. (76)	OP	Human osteoblast-like cells and mice	Collagen I, OCN, OPN	Aucubin increase cortical bone thickness, bone density and tighter trabecular bone in Dex-induced osteoporotic mouse model, up-regulates the expression of collagen I, OCN, OPN in cells.
Gu, et al. (77)	OP	Wistar rats	BMD, BMP2, Runx2, Collagen I, ALP	Anti-Osteoporosis Decoction (AOD) and Yougui Pill treatment effectively inhibits osteoporosis and reduces the broken trabecular bones, increases the level of BMD, ALP levels, accompanied by the increased expressions of BMP2, Runx2, Collagen I and OPN.
Zeng, et al. (78)	OP	Human bone marrow mesenchymal stem cells	Runx2, OCN, and OPN	Artesunate promotes osteoblasts differentiation related proteins Runx2, OCN and OPN expression through activating the Wnt signaling pathway in hBMSCs.
Dong, et al. (79)	OP	Mouse preosteoblast cell lines (MC3T3-E1)	ALP, OCN, OPN, and BMP2	Anagliptin significantly increased matrix deposition and mineralization by osteoblasts, as evidenced by elevated levels of ALP, OCN, OPN, and BMP2.
Lei, et al. (60)	OP	C57B/L6 mice and osteoclasts	Runx2, OPN, TRAP	MLN64 was over-expressed during the process of osteoclast differentiation, up-regulation Runx2 and OPN. The in vivo study suggested that MLN64 deletion reversed streptozotocin-induced trabecular deleterious effects and stimulated bone remodeling.
Yin, et al. (80)	OP	Zebrafish	ALP, hydroxyproline, and TRAP	Evodiamine (EV) can alleviate dexamethasone-induced osteoporosis through increasing the area of bone formation, the content of hydroxyproline and the expression of ALP and TRAP in zebrafish.
Fan, et al. (81)	OP	Sprague-Dawley rats	BMD, ALP, OCN, BMP2, Runx2, TRAP	Myricetin could increase body weight gain and inhibit Dex-induced reduction in BMD, enhanced ALP activity, upregulated OCN, BMP2 and Runx2 levels accompanied with reduced TRAP activity and CTX level.
Wu, et al. (82)	OP	Human plasma samples	B lymphocyte chemoattractant (BLC) and BMP	Inflammatory cytokines were closely related with OP, BLC, OPN and IGFBP4 are greatly related to the pathogenesis of OP.
Lee, et al. (83)	OP	Female ICR mice	collagen type I, BMP2 and OPN	Osteo-F ameliorated bone loss by increasing bone forming molecules including BMP-2 and OPN in osteoporosis.
Marycz, et al. (84)	OP	MC3T3-E1cell lines	OPN, OCN and ALP	PRHD@MnFe2O4 protect osteoporosis through enhancing the expression of bone remodeling markers including OPN, osteocalcin (OCL) and ALP in pre-osteoblasts.
Shao, et al. (85)	OP	MC3T3-E1 cells	ALP, osteocalcin, OPN and BMP-2	Trelagliptin increased the activity of ALP and promoted osteoblastic calcium deposition. Additionally, Trelagliptin upregulated ALP, osteocalcin, OPN, and BMP2 and Runx2 in MC3T3-E1 cells.