Rheumatology Advance Access originally published online on May 2, 2006
Rheumatology 2006 45(12):1529-1533; doi:10.1093/rheumatology/kel111
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A case of chondromatosis indicates a synovial stem cell aetiology
Centre for Biomaterials & Tissue Engineering, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TN, 1Division of Clinical Sciences South, University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield S10 2JF, 2Section of Functional Genomics, Division of Genomic Medicine, University of Sheffield Medical School, E-Floor, Beech Hill Road, Sheffield S10 2RX and 3Department of Orthopaedic Surgery, Northern General Hospital, Sheffield S5 7AU, UK.
Correspondence to: Aileen Crawford, Centre for Biomaterials and Tissue Engineering, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK. E-mail: a.crawford{at}sheffield.ac.uk
Objective. To evaluate cell cultures derived from intrasynovial nodules from a patient with primary synovial chondromatosis (PSC) for aberrant numbers/differentiation of osteochondroprogenitor cells.
Methods. Cell cultures were established from PSC synovial nodules, or normal bovine or human osteoarthritis (OA) synovia (for comparison). Multi-lineage potential was determined using well-characterized in vitro culture systems to assess osteogenic, chondrogenic and adipogenic capability.
Results. Primary PSC cell cultures were typically fibroblastic but contained islands of dense cell clusters/nodules, some of which were isolated and cultured separately [putative osteochondroprogenitris (pOCP) cultures]. OA synovial cultures had barely detectable levels of alkaline phosphatase (AP) that increased (0.006±0.008 to 0.141±0.000 nmol p-nitrophenol/min/cm2) with dexamethasone treatment. AP activity was higher in primary PSC cell cultures and further enhanced by dexamethasone (from 0.076±0.022 to 5.735±0.000 nmol p-nitrophenol/min/cm2). Histochemically, AP was localized as discreet areas within PSC cultures. No AP activity was detected histochemically in OA or normal bovine synovial cultures. The pOCP cultures had high basal AP (5.036±0.439 nmol p-nitrophenol/min/cm2) and spontaneously formed mineralized nodules, which increased in number under standard osteogenic conditions. Under chondrogenic conditions, micromass or pellet-cultured pOCP cells spontaneously synthesized a matrix containing glycosaminoglycans and collagen II. In adipogenic medium, the number of lipid-containing cells was increased.
Conclusions. Compared with cultures established from OA or normal synovia, cell cultures established from PSC synovial nodules were enriched in osteochondroprogenitors, which, unlike normal mesenchymal cells, differentiated along chondrogenic and osteogenic lineages in the absence of dexamethasone.
KEY WORDS: Primary synovial chondromatosis, Disease aetiology, Stem cells, Osteochodroprogenitors, Mesenchymal progenitors, Chondrogenesis, Osteogenesis.