Table 2.

Summary of Possible Causes of Osteoarthritis.

Possible Cause	Specific Effect	Clinical Result	Reference Number
Matrix Degenerating Enzymes	Overproduction of matrix metalloproteinase 13 (MMP-13)	Enzymatic destruction of the extracellular matrix	Zhang et al. [2] Freitag et al. [36]
	Production of other disintegrin enzymes	Enzymatic destruction of the extracellular matrix	Zhang et al. [2] Freitag et al. [36]
Exaggerated Immune Response	Mobilization of macrophages	Catabolic processes	Haseeb and Haqqi [17]
	Cytokine production	Presence of IL-1β and TNF-α, which trigger catabolic and degradative processes	Haseeb and Haqqi [17] Djouad et al. [36]
	A decrease in the TGF-β level	Increased osteophyte formation	Haseeb and Haqqi [17] Djouad et al. [36]
Catabolic and Inflammatory Mediators	Overproduction of cytokines and nitric oxide	Creation of Reactive Oxygen Species (free radicals) that cause oxidative and inflammatory stress	Mortellaro [9]
	Overproduction of proteolytic enzymes	Leads to cartilage breakdown	Mobasheri et al. [4] Jiang et al. [11]
	The activation of toll like receptors (TLRs)	Upregulation of TLR-2 and TLR-4, which activates catabolic pathways in chondrocytes	Haseeb and Haqqi [17] Freitag et al. [36]