The Effects Of Osteoclast Cell And OPG/RANK/RANKL System On Bone Destruction Of Psoriatic Arthritis

Part OneObjective: To summary the clinical, laboratory examination and imagine features of psoriatic arthritis, aim to provide some clinical evidence to distinguish PsA from other arthritis.Method: Collected180cases of psoriatic arthritis from Huashan Hospital during September2007and October2010. Patients medical history, physical examination and laboratory examination and imaging datas were collceted and analysed retrospectively, and therefore the aspects in its epidemiology, family history and past history of Psoriasis were discussed in this study. Moreover, the clinical manifestations of PsA are concluded, results of the laboratory examination were analysed.Results: Among180cases of Psoriatic arthritis, sex ratio of male to female was1.69:1, and the initial onset of this disease could occur at17years old as youngest, the oldest could be76years old, the average age was40.9±12.1years old. The course of skin lesion was6months to45years, the average course was12.7±10.4years; and the course of arthritis was1month to26years, and the average course was4.6±5.7years. The manifestation of skin lesions was prior to arthritis in142cases, the occurrence of arthritis was prior to skin lesions in23cases, and both two kinds of symptoms appeared simultaneously in15cases.The characters of PsA which antedated PS were analysed. People were mostly yong men, the rate of axial joints involved was60.7%, the positive rate of HLA-B27was29.4%, they might have family gathered tendency, more bone destruction and nail abnormalities. Among the dermal-related damages as initial presentation was psoriasis vulgaris (PV), pustular psoriasis was rare.There were22.2%of patients with family history of PV, and these patients onset were early than those without family history. Asymmetrical oligoarthritis and distal interphalangeal arthritis were the commonest feature. While studying the correlations between HLA-B27and axial bones, the implication of damages to sacroiliac joints were more likely to be found in HLA-B27positive patients in comparison to the HLA-B27negative patients. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated in most cases, and the rheumatoid factor and anti-CCP were positive in several cases, but there was no significantly different between the healthy person. Bone destruction and hyperplasia were coexisted in the imaging. There were no correlation between the imaging manifestation and the clinical, lab examines. In the first year58cases of patients had changes in radiology.Conclusion: PsA can affect both sex. Initial symptoms were most commonly present as dermal-related damages. However joint-related damages as PsA should not be ignored. In dermal-related damages, PV was the commonest type, the skin lesion can affeced generally or partly. Although not all patients had family history of PS, but patients with family history had much earlier onset compared with those without family history. Asymmetrical oligoarthritis are the commonest clinical type.There were no typical findings in laboratory examinations, many patients could present with high levels of ESR and CRP. The positive rate of rheumatoid factor had no difference with healthy control. In early imaging could see bone destruction, and bone hyperplasia could emerge as the diease progressed. But the physical and lad examinations could not assess the bone destruction of joints.Part TwoObjective: To explore the changes of OC, TNF-a and OPG/RANK/RANKL system in the patients of PsA.Method: The peripheral blood mononuclear cells from41cases of PsA patients,20cases of OA patients and24cases of healthy controls were cultured in the medium containing macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB-ligand (RANKL). After being cultured for14days, cytochemistry was applied to detect tartrate-resistant acid phosphatase (TRAP) expression and the cells with positive TRAP and≥3nuclei were counted and defined as OC. At the same time, ELISA was used to measure serum TNF-a and OPG/RANK/RNAKL system levels in all cases.The differences were analyzed among PsA,OA and the healthy controls. Devide the PsA group into bone destruction group and no destruction group, into higher activity group and lower activity group. Compared the differences between the two groups. Analysed the correlations between the imaging scores and the levels of OC, OPG/RANK/RANKL system et al.Results: Significantly higher OC production were observed in peripheral blood of PsA patients(17.7±4.8/view field) than that of the healthy controls (6.4±1.6/view field)and OA patients(6.5±1.6/view field), there were no difference in morphology of the OC. The levels of TNF-a were significantly higher in PsA patients(125.0±78.6pg/ml) than in other two groups; the same to the levels of RANKL(178.3±38.0pg/ml); but there were no difference in OPG levels; and the levels of OPG/RANKL were significantly lower in PsA groups(0.5±0.1).There were significantly difference between the bone destruction group and no destruction group in the levels of OC, TNF-a, RANKL and OPG/RANKL P<0.05-0.01); but in higher activity group only TNF-a were higher (P<0.01), others had no difference compared to the lower activity group. Imaging scores had positive correlation with the levels of OC and RANKL (P<0.05), and no correlation with the levels of OPG/RANKL、TNF-a、ESR and CRP. Conclusion: In PsA, there were more osteoclast precursor cells in peripheral blood and higher serum level of TNF-a and RANKL, but lower level of OPG/RANKL. Imaging scores were closely related with the levels of RANKL and the the numbers of OC, but no significant correlation with disease activity. It was not comprehensive to judge disease severity only according to clinical manifestations and laboratory parameters. OC and RANKL were more valuable to identify bone destruction, because they were not affected by the impact of the clinical conditions.Part ThreeObjective: To explore the changes of TNF-a, OC and OPG/RANK/RANKL system after the treatment of TNF-a blocker in PsA patientsMethod: Collected8cases of psoriatic arthritis from Huashan Hospital during March2010and February2011. All patients were treateted with TNF-a blocker. Medical history, laboratory examinations and imaging scores were collceted and analysed. All patients blood were collected, and the levels of OC, TNF-a and OPG/RANK/RAKL system were measured before and aftert the treatment3months later. Analysed the correlation of OC, OPG/RANK/RANKL systems with diease activity and imaging scores et al.Results: After TNF-a blocker treatment, all patients clincal features and laboratory examinations were decreased obviously (P<0.05). Compared with baseline, the levels of TNF-a, OC and RANKL in PsA were decreased, OPG/RANKL were increased(P<0.01). The levels of OC and RANKL were obviously correlated with disease activity (P<0.05), and their levels were obviously correlated with imaging scores too (P<0.05), but the levels of TNF-a showed no correlation with the imaging scores. The the ratio of OPG to RANLKL was decreased, promoting the activity of OC, strengthen the ability of bone destruction in PsA.Conclusion: There was positive correlationship between RANKL and OC. TNF-a blocker might inhibit the capability of PBMCs’ differentiating into OC and work through OPG/RANK/RANKL systems to prevent the occurrence of bone destruction. OC and RANKL could not only reflect the levels of TNF-a but also reflect the changes in imaging scores. It was a practical, effective clinical indicator to judge the curative effect of TNF-a blocker.