Table 1.

The features of the four identified OA subtypes

Features	C1: GAG metabolic disorder	C2: Collagen metabolic disorder	C3: Activated sensory neurons	C4: Inflammation
Molecular features	PCOL CE2/ACAN ↑ VCAN ↓ GAG metabolic ↑	TFGB/COL6A1 ↑ Collagen catabolic ↑	GRIK2/GRM7↑ Synapse assembly ↑	TMSB4X/CD34 ↑ Immune response ↑
Clinical features	Typical symptom	Severe osteophyte	Younger age of KRS	Apparently narrow joint space
Treatment principles	GAG supplement	Collagen supplement	Analgesia	Anti-inflammation
Drugs	Hyaluronic acid Hyaluronic Glucosamine	Gelatin Hyaluronic collagen Undenatured collagen	NGF-inhibitor (tanezumab) Acetaminophen Opioids	NSAIDs Corticosteroids IL-1 inhibitor (canakinumab) TNF-α inhibitor (adalimumab, infliximab, etanercept)