Objective. We aimed to investigate the expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) on chondrocytes from human healthy and osteoarthritic cartilage. Methods. We recruited 12 patients with osteoarthritis (OA) undergoing surgical knee replacement. Articular cartilage was split into two zones showing macroscopically and histologically the lowest (MIN) and highest (MAX) degree of osteoarthritic damage. Additional specimens of cartilage were obtained from three healthy donors. Chondrocytes were isolated by enzymatic digestion and freshly processed for NGF protein, Trk A detection and mRNA extraction. NGF‐β mRNA was determined by a reverse transcriptase–polymerase chain reaction (RT–PCR). NGF‐β and TrkA expression was evaluated by immunofluorescence and flow cytometry analysis. Results. NGF‐β‐specific mRNA was detected in normal and osteoarthritic chondrocytes. NGF‐β protein levels were low in normal chondrocytes, increased in MIN osteoarthritic cartilage and further enhanced in MAX osteoarthritic cartilage. Likewise, TrkA was scarcely expressed on normal chondrocytes and progressively increased on osteoarthritic chondrocytes based on the extent of anatomic damage. Conclusions. This is the first study showing that human chondrocytes synthesize NFG‐β and express on their surface the high affinity NGFR (p140 TrkA). Of note, NGF‐β and TrkA were upregulated in osteoarthritic chondrocytes suggesting a role of NGF in the pathophysiology of OA. We can speculate that NGF, like other growth factors, stimulates chondrocyte metabolism in the osteoarthritic process.

Scleroderma renal crisis (SRC) occurs in 5–10% of SSc patients, who may present with an abrupt onset of hypertension, acute renal failure, headaches, fevers, malaise, hypertensive retinopathy, encephalopathy and pulmonary oedema. Patients at greatest risk of developing SRC are those with diffuse cutaneous or rapidly progressive forms of SSc, and treatment with a recently commenced high dose of corticosteroid. Laboratory tests may demonstrate hypercreatinaemia, microangiopathic haemolytic anaemia (MAHA), thrombocytopaenia and hyperreninaemia. Renal crisis is also linked to a positive ANA speckled pattern, antibodies to RNA polymerase I and II, and an absence of anti-centromere antibodies. Early, aggressive treatment with angiotensin-converting enzyme inhibitors has improved prognosis in SRC, although 40% of the patients may require dialysis, and mortality at 5 yrs is 30–40%. Median time to recovery is 1 yr, and typically occurs within 3 yrs. Prognosis is worse for males, but may not be related to corticosteroid use, presence of MAHA or severity of renal pathology. Modification of endothelin over-activity, which is implicated in the pathogenesis of SRC, may offer a future therapeutic approach.