Table III.

Lubricin supplementation in the OA joint. ACLT – anterior cruciate ligament transection, HDV – helper dependent adenoviral vector, OA – osteoarthritis, OARSI – osteoarthritis research society international, PTOA – post-traumatic osteoarthritis, IL-1ra – interleukin 1 receptor antagonist, IA – intraarticular, DMM – destabilization of the medial meniscus, AC – articular cartilage, DNIIR – dominant-negative mutant of TGF|3R2 (OA model), OVX – ovariectomized rat model, rhPRG4 – recombinant human lubricin/proteoglycan 4, MMP-13 – matrix metalloproteinase 13, TRAP – tartrate-resistant acid phosphatase, HSL – human synoviocyte lubricin, HSFL – human lubricin, GAG – glycosaminoglycans, CTX-II – carboxy-terminal telopeptides of type II collagen, MT – meniscal tear, ASI – aggrecanase specific inhibitor, MUM – monosodium urate monohydrate, hrs – hours, HA – hyaluronic acid, PBS – phosphate buffered saline.

	Species	Model	Treatment	Outcome following lubricin supplementation
6	Mouse	ACLT	Prg4 overexpression in cartilage (Col21a promoter) or Prg4 via HDV	Prg4 overexpression decreased signs of age-related and post-traumatic OA, including preservation of cartilage volume, decreased OARSI score, increased expression of Col10a1 and Mmp13 and decreased functional impairment; gene transfer with HDV-Prg4 protected against PTOA and age-related OA based on decreased OARSI score and increased cartilage volume
68	Mouse	ACLT	Prg4 over-expression in cartilage (Col21a promoter) or Prg4 ± Il-1Ra via HDV	Prg4 overexpression reduced age-related and post-traumatic OA; Prg4 expression inhibited transcriptional programs that promote cartilage catabolism and hypertrophy; IA injection of HDV expressing Prg4 protected against PTOA
69	Mouse	ACLT	IA HDV-Prg4 or 10mabHDV-Prg4	Both treatments improved OARSI scores and increased cartilage volume and surface area; 10mabHDV-Prg4 treated joints had lower OARSI scores and larger bone area covered by cartilage than HDV-Prg4 treated joints
70	Mouse	ACLT or DMM	IA HDV-NFκB-Il1ra and/or HDV-EF1-Prg4	Combined therapy increased expression of pro-anabolic and cartilage matrix genes; decreased catabolic gene and inflammatory mediator expression; preserved AC volume and surface area; prevented thermal hyperalgesia
71	Mouse	DNIIR	Prg4 overexpression via Col2a1 promoter	Fewer missed steps; decreased cartilage fibrillation and OARSI scores; increased cartilage thickness
72	Rat	OVX	IA rhPRG4 at day 0or14	Decreased cartilage degeneration, OARSI score, proteoglycan loss, and staining for collagen X and MMP-13; increased lubricin expression; normalized bone remodeling; inhibited elevation of TRAP and Osterixpositive cells; rescued thickening of calcified cartilage zone; decreased vascular invasion of calcified cartilage
73	Rat	DMM	IA rhPRG4 1 or 3x/wk	Decreased cartilage degeneration and cartilage lesion/degeneration width; facilitated boundary lubrication and decreased synovial cell adhesion; 3x/wk dosing increased benefit
74	Rat	ACLT	IA HSL or rhPRG4 or purified HSFL	Decreased OARSI scores; increased lubricin staining and Prg4 expression; decreased fibrillation at cartilage surface with more superficial chondrocytes; decreased collagen type II degradation; no difference between treatments
75	Rat	ACLT	IA HSL	Equalized weight distribution between hind legs; increased lubricin mRNA expression; increased lubricin staining to level of sham-operated joints; increased GAG content; decreased urinary CTX-II; OARSI score not different
76	Rat	MT	IA rhPRG4 ± ASI	Decreased pain 4 wks post-injury and for 3 wks post-dose cessation; combined therapy decreased pain more than monotherapy
77	Rat	MUM	IA rhPRG4	At 6 h: supplementation normalized weight bearing and myeloperoxidase activity. At 24 h: no difference
78	Rat	ACLT	IA purified HSFL ± HA	Decreased radiographic and histologic OA scores, increased SF [lubricin]; HA provided no added benefit
27	Rat	ACLT	IA rhPRG4	Increased lubricin staining in articular cartilage post-injury; decreased caspase-3 and MMP-13 staining
26	Rat	ACLT	IA purified HSFL ± exercise	Increased lubricin staining in articular cartilage; increased SF [lubricin]; decreased urinary CTX-II levels and caspase-3 staining
79	Pig	DMM	IA rhPRG4 ± HA	Decreased macroscopic OA scores; increased SF [lubricin]; decreased serum IL-1β; no difference between PBS and rhPRG4 + HA