Table 1. Major Topics and Findings in the Biology of OA: 2013.

Topic	New Findings	Therapeutic Implications	References
Epigenetics	↓ methylation of MMP-13, IL-1β, and iNOS promoters. ↑ methylation of Sox-9 promoter. Altered histone acetylation and differential miRNA expression in OA chondrocytes.	Histone deacetylase inhibitors decrease OA in a mouse model of OA. DNA methylation and miRNA expression will be much more difficult to target for therapy.	2-13
Wnt Signaling	Sclerostin present in articular cartilage. ↑Dkk-1 in OA cartilage and synovium. ↑WISP-3/CCN6 in OA cartilage.	Sclerostin inhibition/deletion did not affect the development of OA in rat or mouse models. Inconclusive results with Dkk-1 inhibition/overexpression or manipulation of Wnt/β-catenin activity.	14-20
Inflammatory Factors	Production of multiple pro-inflammatory mediators by the injured meniscus. S100A8 and S100A9 present in OA synovium. Plasma proteins and soluble CD14 present in SF which activate TLRs. CCL2→CCR2 involved in pain in OA.	↓ OA in S100A8/A9 -/- mice in collagenase-induced OA but not in DMM model. ↓ pain but not OA in CCR2 -/- mice in the DMM model	21-28
Lubricin (PRG4)	Important boundary lubricant that protects articular surface.	Overexpression of lubricin reduces OA severity in mouse models of OA.	29-32
FGF Signaling	Balance of FGFR1 to FGFR3 mediated signaling determines catabolic vs anabolic activity of FGFs.	Less severe OA in FGFR1-/- mice. Activation of FGFR3 by FGF-18 more likely to reduce OA than FGFR1 activation by FGF-2.	33-40
Bone	Correlation between cartilage and bone changes in OA varies by model system studied, particularly when osteophytes are examined.	Subsets of OA where bone is a driving factor appear most likely. Inhibition of cathepsin K ↓OA severity in rabbit and mouse models.	14, 41-48.