Interactions between tenocytes and monosodium urate monohydrate crystals: implications for tendon involvement in gout.
OBJECTIVE
Advanced imaging studies have demonstrated that urate deposition in periarticular structures, such as tendons, is common in gout. The aim of this study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on tenocyte viability and function.


METHODS
The histological appearance of tendons in joints affected by advanced gout was examined using light microscopy. In vitro, colorimetric assays and flow cytometry were used to assess cell viability in primary rat and primary human tenocytes cultured with MSU crystals. Real-time PCR was used to determine changes in the relative mRNA expression levels of tendon-related genes, and Sirius red staining was used to measure changes in collagen deposition in primary rat tenocytes.


RESULTS
In joint samples from patients with gout, MSU crystals were identified within the tendon, adjacent to and invading into tendon, and at the enthesis. MSU crystals reduced tenocyte viability in a dose-dependent manner. MSU crystals decreased the mRNA expression of tendon collagens, matrix proteins and degradative enzymes and reduced collagen protein deposition by tenocytes.


CONCLUSIONS
These data indicate that MSU crystals directly interact with tenocytes to reduce cell viability and function. These interactions may contribute to tendon damage in people with advanced gout.
Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.
Ashika
A
Chhana
Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.
Karen E
KE
Callon
Department of Histology, Waikato Hospital, Hamilton, New Zealand.
Michael
M
Dray
Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.
Bregina
B
Pool
Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.
Dorit
D
Naot
Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.
Greg D
GD
Gamble
Department of Orthopaedic Surgery, Middlemore Hospital, Auckland, New Zealand.
Brendan
B
Coleman
Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Geraldine
G
McCarthy
Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
Fiona M
FM
McQueen
Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.
Jillian
J
Cornish
Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.
Nicola
N
Dalbeth
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006073:Gout / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D045726:Metalloproteases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013710:Tendons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D014527:Uric Acid / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*
D012333:RNA, Messenger; D014527:Uric Acid; D003094:Collagen; D045726:Metalloproteases
Disease Activity; Gout; Tendinitis