Table IV.

Phenotype and treatment effect of lubricin-null mouse models. Mo – month, AC – articular cartilage, SZ – superficial zone, wk – week, COF – coefficient of friction, MFC – medial femoral condyle, OA – osteoarthritis, WT – wild type, HTZ – heterozygote, IA – intra-articular, PTH – parathyroid hormone, SDF-1 – stromal cell-derived factor 1, FGF-2 – fibroblast growth factor-2, CTX-II – carboxy-terminal telopeptides of type II collagen.

	Model	Treatment	Outcome/Phenotype
11	Prg4 null mice	None	Normal joints at birth. At 2–4 mo: abnormal protein deposition on AC; decreased SZ chondrocytes; synovial hyperplasia; abnormal calcification of tendons/sheaths
23	Prg4 null mice	None	Normal joints at birth. At 2 wks: irregular cartilage surface with disruption of parallel orientation of collagen fibrils; absence of lamina splendens. At 1 mo: increase in joint COF
24	Prg4 null mice	None	At 2 wks: Roughened cartilage surface. At 16 wks: decreased pericellular proteoglycans; increased COF. Adult: lower elastic modulus in articular cartilage
80	Prg4 null mice	None	At 10 wks: decreased live chondrocyte volume fraction in MFC; increased cartilage thickness in MFC, increased caspase-3 positive cells in MFC superficial and upper intermediate cartilage zones
81	Prg4 null mice	Prg4 genetically restored at pre-conception or 3 wk, 2 mo, or 6 mo of age	Rx: no joint disease with pre-conception restoration of Prg4; 3 wk restoration: increased caspase-3 activation and histological evidence of OA; 2 & 6 mo restoration: unchanged from Prg4 null littermates
82	Prg4 null mice	Prg4 genetically restored at7or14 days of age	Rx: restored joints unchanged from null joints in COF and histology; restored cartilage had decreased numbers of peroxynitrite and caspase-3 positive cells
83	Prg4 null mice	Cyclic loading	COF of null joints higher than WT or HTZ; Rx: upto4h of cyclicjoint loading increased null joint COF while WT and HTZ COF remained unchanged. At 26 h: all COF increased (larger increases in null and HTZ joints)
84	Prg4 null mice	IA human lubricin	Null joints showed mitochondrial dysregulation-mediated caspase activation and increased levels of peroxynitrite and superoxide; Rx: treatment prevented caspase-3 activation in AC and decreased whole joint friction
85	Prg4 null mice	PTH	Null mice showed increased peripheral blood neutrophils; decreased marrow B-lymphocytes; decreased SDF-1; Rx: PTH normalized findings
86	Prg4 null mice	PTH	Young: decreased growth plate hypertrophic zone height, trabecular bone, and serum bone formation markers; Adult: decreased trabecular and cortical bone, decreased tarsal range of motion, decreased liver and bone marrow FGF-2 mRNA; Rx: Young: no change; Adult: PTH increased bone mass and normalized FGF-2 mRNA
87	Prg4 null mice	PTH	Acellular material deposited on AC and menisci; increased AC degradation; increased serum [CTX-II]; decreased articular chondrocyte apoptosis; increased SDF-1 expression in synovium; irregularly contoured subchondral bone; Rx: PTH induced a secondary deposit overlaying the acellular material on the AC