Impact of proteoglycan-4 and parathyroid hormone on articular cartilage.
Proteoglycan-4 (Prg4) protects synovial joints from arthropathic changes by mechanisms that are incompletely understood. Parathyroid hormone (PTH), known for its anabolic actions in bone, increases Prg4 expression and has been reported to inhibit articular cartilage degeneration in arthropathic joints. To investigate the effect of Prg4 and PTH on articular cartilage, 16-week-old Prg4 mutant and wild-type mice were treated with intermittent PTH (1-34) or vehicle control daily for six weeks. Analyses included histology of the knee joint, micro-CT of the distal femur, and serum biochemical analysis of type II collagen fragments (CTX-II). Compared to wild-type littermates, Prg4 mutant mice had an acellular layer of material lining the surfaces of the articular cartilage and menisci, increased articular cartilage degradation, increased serum CTX-II concentrations, decreased articular chondrocyte apoptosis, increased synovium SDF-1 expression, and irregularly contoured subchondral bone. PTH-treated Prg4 mutant mice developed a secondary deposit overlaying the acellular layer of material lining the joint surfaces, but PTH-treatment did not alter signs of articular cartilage degeneration in Prg4 mutant mice. The increased joint SDF-1 levels and irregular subchondral bone found in Prg4 mutant mice introduce novel candidate mechanisms by which Prg4 protects articular cartilage.
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
Chad M
CM
Novince
Payam
P
Entezami
Christopher G
CG
Wilson
Jason
J
Wang
Seo
S
Oh
Amy J
AJ
Koh
Megan N
MN
Michalski
Benjamin P
BP
Sinder
Kenneth M
KM
Kozloff
Russell S
RS
Taichman
Laurie K
LK
McCauley
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D019902:Chondrocytes / Q000473:pathology; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008592:Menisci, Tibial / Q000473:pathology; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011509:Proteoglycans / Q000172:deficiency / Q000378:metabolism*; D000099158:Proteoglycan 4
D054377:Chemokine CXCL12; D010281:Parathyroid Hormone; D011509:Proteoglycans; C515256:Cxcl12 protein, mouse; C498837:Prg4 protein, mouse; D000099158:Proteoglycan 4