Spinal pigmented villonodular synovitis and tenosynovial giant cell tumor: A report of two cases and a comprehensive systematic review.

BACKGROUND AND OBJECTIVE: Pigmented villonodular synovitis (PVNS) is a lesion of uncertain etiology that involves the synovial membranes of joints or tendon sheaths, representing a diffuse and non-encapsulated form of the more common giant cell tumors of the synovium (GCTTS). PVNS was reclassified to denote a diffuse form of synovial giant cell tumor (TSGCT), while 'giant cell tumor of the tendon sheath (GCTTS)' was used for localized lesions. These pathologies rarely affect the axial skeleton. We provide an unprecedented and extensive systematic review of both lesions highlighting presentation, diagnostic considerations, treatment, prognosis, and outcomes, and we report a short case-series. METHOD: We describe two-cases and conduct a systematic review in accordance with PRISMA guidelines. RESULT: PVNS was identified in most of the cases reviewed (91.6 %), manifesting predominantly in the cervical spine (40 %). Patients commonly presented with neck pain (59 %), back pain (53 %), and lower back pain (81.2 %) for cervical, thoracic, and lumbar lesions, respectively. GTR occurred at rates of 94 %, 80 %, and 87.5 %. Recurrence was most common in the lumbar region (30.7 %). GCTTS cases (8%) manifested in the cervical and thoracic spine at the same frequency. We reported first case of GCTTS in the lumbosacral region. Both poses high rate of facet and epidural involvements. CONCLUSION: Spinal PVNS and GCTTS are rare. These lesions manifest most commonly as PVNS within the cervical spine. Both types have a high rate of facet and epidural involvement, while PVNS has the highest rate of recurrence within the lumbar spine. The clinical and radiological features of these lesions make them difficult to differentiate from others with similar histogenesis, necessitating tissue diagnosis. Proper management via GTR resolves the lesion, with low rates of recurrence.

Pigmented villonodular synovitis does not influence the outcomes following cruciate-retaining total knee arthroplasty: a case-control study with minimum 5-year follow-up.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare synovial disease with benign hyperplasia, which has been successfully treated with total knee arthroplasty (TKA). The purpose of this study was to investigate the middle-term follow-up outcomes of cruciate-retaining (CR) TKA in patients with PVNS. METHODS: From January 2012 to December 2014, a retrospective study was conducted in 17 patients with PVNS who underwent CR TKA as PVNS group. During this period, we also selected 68 patients with osteoarthritis who underwent CR TKA (control group) for comparison. The two groups matched in a 1:4 ratio based on age, sex, body mass index, and follow-up time. The range of motion, Knee Society Score, revision rate, disease recurrence, wound complications, and the survivorship curve of Kaplan-Meier implant were assessed between the two groups. RESULTS: All patients were followed up at least 5 years. There was no difference in range of motion and Knee Society Score between the two groups before surgery and at last follow-up after surgery (p > 0.05). In the PVNS group, no patients with the recurrence of PVNS were found at the last follow-up, one patient underwent revision surgery due to periprosthetic fracture, and three patients had stiffness one year after surgery (17.6% vs 1.5%, p = 0.005; ROM 16-81°), but no revision was needed. At 7 years, the implant survivorship was 90.0% in the PVNS group and 96.6% in the control group (p = 0.54). CONCLUSIONS: This study demonstrated that the function of patients with PVNS who underwent CR TKA had been significantly improved, and the survival rate of implants in these patients was similar to the patients with OA. Consequently, the patients with PVNS who underwent CR TKA might be an achievable option. However, these patients should pay more attention to the occurrence of postoperative stiffness complications.

Spontaneous swelling of the ankle in a child : a difficult diagnosis.

The authors present a case of monoarticular localized pigmented villonodular synovitis (PVNS) in a 7-year old girl. PVNS is a rare benign disease of the synovial tissue. It is especially rare in ankles of children, with only 15 cases reported in literature. The girl presented with swelling and pain in the left ankle since 4 weeks. The tentative diagnosis was made after a joint puncture and a MRI scan. A synovial mass with a brown-yellowish appearance was seen during the excisional biopsy. After removing the entire mass and without adjuvant therapy, no recurrence was detected after 12 months. As it is very rare in children, PVNS is easily misdiagnosed. Early diagnosis is important to prevent bone and cartilage damage. A review of the clinical, radiological and therapeutical features of PVNS are presented.

Modified Lemaire extra-articular stabilisation of the knee for the treatment of anterolateral instability combined with diffuse pigmented villonodular synovitis: a case report.

BACKGROUND: Diffuse pigmented villonodular synovitis (PVNS) of the knee is a rare proliferative joint disease associated with high recurrence rates following surgical treatment. Intra-articular joint instability in conjunction with PVNS implies complex reconstructive strategies due to the destructive nature of the disease. CASE PRESENTATION: Here, we present the case of a young patient with refractory PVNS and a chronic ipsilateral anterior cruciate ligament (ACL) rupture. Clinically, the patient presented with a grade 3 pivot shift phenomenon, indicating anterolateral rotational instability. Usually, PVNS implies a contraindication for ACL reconstruction due to the degenerative and pro-inflammatory joint microenvironment that is induced and maintained by PVNS. Therefore, we have performed a modified Lemaire extra-articular stabilization resulting in significant clinical improvement and subjective joint stability. In the latest follow-up examination at 12 months, the patient reported subjective joint stability and no swelling. In the clinical examination, the patient showed dynamic joint stability during walking. Additionally, the patient presented with grade 0 in pivot-shifting compared to the contralateral knee. The Lachman test exhibited no increased side-to-side difference and a firm endpoint. CONCLUSIONS: Extra-articular anterolateral stabilisation of the knee in patients having anterolateral knee instability combined with PVNS is a safe and efficient surgical treatment option yielding significant clinical improvement as well as subjective joint stability.

Long-term outcome of pigmented villonodular synovitis of the hip after joint preserving therapy.

INTRODUCTION: Pigmented villonodular synovitis (PVNS) is a rare, destructive synovial disease that affects the hip joint the second most common after the knee. However, in contrast, joint preserving surgery in the hip joint is considered to be significantly more difficult or even impossible due to earlier occurrence of osteochondral dissemination and surgical difficulties. Today, earlier diagnosis due to the generous use of MRI and modern surgical strategies raise hope for improved outcomes. METHODS: Since 2005, six patients with PVNS of the hip and a minimal follow-up of 2 years underwent joint preserving surgery in our institution (mean age 20.5 years, range 14-27). After PVNS was suspected in the MRI and confirmed by arthroscopic biopsy (four diffuse, two focal forms), synovectomy was carried out in 5 patients via surgical hip dislocation and in one focal case via arthroscopy. In diffuse forms, adjuvant radiosynoviorthesis (RSO) was conducted 6-8 week postoperatively. MRI and clinical examinations were performed during follow-up. RESULTS: After a mean follow-up of 8 years (range 35-141 months), five of six patients did not show recurrence or secondary osteoarthritis. Clinical outcome evaluation resulted in a mean modified Harris Hip Score of 91 points (range 67-100 points). A 21-year-old patient with a diffuse form and advanced osteochondral involvement at the time of diagnosis was eventually treated by total hip arthroplasty. CONCLUSION: In cases without osteochondral involvement, recurrence-free long-term results without progression of joint degeneration can be achieved by joint preserving therapy.

Multi-lineage differentiation and angiogenesis potentials of pigmented villonodular synovitis derived mesenchymal stem cells--pathological implication.

Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation characterized by its hyper-vascularity within the lesion. The true etiology and cell source of this disease entity still remain unclear. Mesenchymal stem cells (MSCs) exist in various tissues of human body. However, it has not been clarified whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from PVNS (PVNS-SCs), and by comparing to the MSCs from normal synovium (Syn-SCs) of the same individual, we investigated whether PVNS-SCs differed in the capacity for multi-differentiation and inducing angiogenesis. We first demonstrated that PVNS-SCs existed in the lesion of PVNS of three individuals. Moreover, we showed PVNS-SCs had better osteogenic differentiation potential than Syn-SCs, whereas Syn-SCs had better capacity for adipogenic and chondrogenic differentiation. By genome-wide analysis of gene expression profile using a complementary DNA microarray and comparing to Syn-SCs, we identified in PVNS-SCs a distinct gene expression profile characterized by up-regulation of genes involved in angiogenesis. In vitro and in vivo studies further confirmed that PVNS-SCs had better capacities for promoting angiogenesis. In summary, the identification of PVNS-SCs in PVNS tissue and their distinct angiogenic potential may help elucidate the underlying etiology of this disease.

[High recurrence and good functional results after arthroscopic resection of pigmented villonodular synovitis]. / Alta recidiva y buenos resultados funcionales tras la resección artroscópica de la sinovitis villonodular pigmentaria de la rodilla.

INTRODUCTION: Pigmented villonodular synovitis (PVS) is a synovial proliferation disorder of uncertain aetiology, with some controversy as regards its proper treatment. The purpose of the study was to evaluate the functional outcome and recurrence rate in a series of patients diagnosed with both the diffuse and the localised type of PVS and treated by arthroscopic resection. MATERIAL AND METHODS: Twenty-four patients diagnosed with PVS were retrospectively assessed. There were 11 cases with the diffuse type, and 13 cases with the localised type of PVS. They were followed-up for a median of 60 months (range, 34-204). They underwent arthroscopic synovectomy, and were functionally evaluated with IKDC, WOMET, and Kujala scores. RESULTS: There was recurrence in 8 out of 13 (61.5%) cases with the diffuse type of PVS. Two of these patients were treated with radiation. One patient underwent surgical resection with an open procedure due to extra-articular involvement. The remaining 5 patients underwent a second arthroscopic resection, and no recurrence was subsequently observed. Cases with localised PVS did not recur after a single arthroscopic resection. IKDC, WOMET and Kujala scores improved by 30.6, 37.4 and 34.03 points, respectively. DISCUSSION: Pigmented villonodular synovitis treated by arthroscopic resection showed good functional results at mid-term follow-up. A single arthroscopic resection was sufficient to treat the localised PVS, whereas the diffuse type of PVS required a second arthroscopic resection in most cases, due to its high rate of recurrence.

Functional outcome and quality of life after the surgical treatment for diffuse-type giant-cell tumour around the knee: a retrospective analysis of 30 patients.

We retrospectively reviewed 30 patients with a diffuse-type giant-cell tumour (Dt-GCT) (previously known as pigmented villonodular synovitis) around the knee in order to assess the influence of the type of surgery on the functional outcome and quality of life (QOL). Between 1980 and 2001, 15 of these tumours had been treated primarily at our tertiary referral centre and 15 had been referred from elsewhere with recurrent lesions. The mean follow-up was 64 months (24 to 393). Functional outcome and QOL were assessed with range of movement and the Knee injury and Osteoarthritis Outcome Score (KOOS), the Musculoskeletal Tumour Society (MSTS) score, the Toronto Extremity Salvage Score (TESS) and the SF-36 questionnaire. There was recurrence in four of 14 patients treated initially by open synovectomy. Local control was achieved after a second operation in 13 of 14 (93%). Recurrence occurred in 15 of 16 patients treated initially by arthroscopic synovectomy. These patients underwent a mean of 1.8 arthroscopies (one to eight) before open synovectomy. This achieved local control in 8 of 15 (53%) after the first synovectomy and in 12 of 15 (80%) after two. The functional outcome and QOL of patients who had undergone primary arthroscopic synovectomy and its attendant subsequent surgical procedures were compared with those who had had a primary open synovectomy using the following measures: range of movement (114º versus 127º; p = 0.03); KOOS (48 versus 71; p = 0.003); MSTS (19 versus 24; p = 0.02); TESS (75 versus 86; p = 0.03); and SF-36 (62 versus 80; p = 0.01). Those who had undergone open synovectomy needed fewer subsequent operations. Most patients who had been referred with a recurrence had undergone an initial arthroscopic synovectomy followed by multiple further synovectomies. At the final follow-up of eight years (2 to 32), these patients had impaired function and QOL compared with those who had undergone open synovectomy initially. We conclude that the natural history of Dt-GCT in patients who are treated by arthroscopic synovectomy has an unfavourable outcome, and that primary open synovectomy should be undertaken to prevent recurrence or residual disease.

Pigmented villonodular synovitis of the thoracic spine.

Pigmented villonodular synovitis (PVNS) is a proliferative lesion of the synovial membranes. Knees, hips, and other large weight-bearing joints are most commonly affected. PVNS rarely presents in the spine, in particular the thoracic segments. We present a patient with PVNS in the thoracic spine and describe its clinical presentation, radiographic findings, pathologic features, and treatment as well as providing the first comprehensive meta-analysis and review of the literature on this topic, to our knowledge. A total of 28 publications reporting 56 patients were found. The lumbar and cervical spine were most frequently involved (40% and 36% of patients, respectively) with infrequent involvement of the thoracic spine (24% of patients). PVNS affects a wide range of ages, but has a particular predilection for the thoracic spine in younger patients. The mean age in the thoracic group was 22.8 years and was significantly lower than the cervical and lumbar groups (42.4 and 48.6 years, respectively; p=0.0001). PVNS should be included in the differential diagnosis of osteodestructive lesions of the spine, especially because of its potential for local recurrence. The goal of treatment should be complete surgical excision. Although the pathogenesis is not clear, mechanical strain may play an important role, especially in cervical and lumbar PVNS. The association of thoracic lesions and younger age suggests that other factors, such as neoplasia, derangement of lipid metabolism, perturbations of humoral and cellular immunity, and other undefined patient factors, play a role in the development of thoracic PVNS.

Primary arthroscopic synovectomy for pigmented villo-nodular synovitis of the knee: recurrence rate and functional outcomes after a mean follow-up of seven years.

BACKGROUND: Pigmented villo-nodular synovitis (PVNS) is an uncommon proliferative condition of the synovial membrane that chiefly affects the knee. Arthroscopic synovectomy may carry lower morbidity rates but higher recurrence rates than open synovectomy. Here, our objective was to evaluate recurrence rates and functional outcomes after primary arthroscopic synovectomy for PVNS of the knee. HYPOTHESIS: Primary arthroscopic synovectomy preserves knee function while producing low recurrence and complication rates. MATERIALS AND METHODS: We retrospectively included consecutive patients with histologically documented PVNS managed with primary arthroscopic synovectomy at two centres between 1998 and 2011. Twenty-three patients, 13 men and 10 women with a mean age of 41 ± 12 years, were reviewed including 16 patients with nodular and 7 with diffuse form of this disease. Patients with localized disease underwent partial synovectomy and those with diffuse disease complete synovectomy followed by chemical synovectomy of any residual lesions. The primary outcome measure was recurrence. Secondary outcome measures were the Tegner-Lysholm and Ogilvie-Harris scores. RESULTS: Follow-up data were obtained after a mean of 7 ± 4 years in 21 patients (14 with nodular and 7 with diffuse disease), of whom 2 had recurrences, after 2 and 5 years, respectively. At last follow-up, neither patient had any evidence of recurrence. The mean Tegner-Lysholm score was significantly improved (from 68 ± 10 to 90 ± 8, P=0.0004) and the mean Ogilvie-Harris score indicated excellent function (11 ± 1). DISCUSSION: Primary arthroscopic synovectomy ensures satisfactory control of PVNS while preserving knee function. A full recovery remains possible even in patients with diffuse disease. In the event of a recurrence, open synovectomy can be performed.

Tenosynovial giant cell tumor: case report and review.

Tenosynovial giant cell tumors are a group of generally benign intra-articular and soft tissue tumors with common histologic features. They can be roughly divided into localized and diffuse types. Localized types include giant cell tumors of tendon sheath and localized pigmented villonodular synovitis, whereas diffuse types encompass conventional pigmented villonodular synovitis and diffuse-type giant cell tumor. Localized tumors are generally indolent, whereas diffuse tumors are locally aggressive. Recent developments indicate that tenosynovial giant cell tumors are clonal neoplastic tumors driven by overexpression of CSF1. Herein, I report a case of intra-articular, localized tenosynovial giant cell tumor (or localized pigmented villonodular synovitis) and review the classification, histopathology, and recent developments regarding its pathogenesis.

Long-term results of surgical treatment of pigmented villonodular synovitis of the knee.

OBJECTIVES: The aim of this study was to evaluate the long-term results of total synovectomy in pigmented villonodular synovitis of the knee (PVNS). METHODS: Open total synovectomy was performed for 19 patients (9 men, 10 women; mean age: 42.8 years) with PVNS. Of these patients, 15 had diffuse and 4 localized PVNS. The patients were followed for an average of 80.2 months and the average time between the onset of complaints and surgery was 23 months. In 4 patients, PVNS was identified during total knee replacement (TKR) performed due to gonarthrosis. Radiotherapy was performed as an adjuvant treatment in one patient with recurrence. Puncture was performed in 11 patients due to effusion and 8 to 70 cc of fluid was aspirated. Diagnosis was made during the exposure for TKR in 4 patients, by a biopsy in 2 and based on joint puncture and MRI findings in the rest. RESULTS: Recurrence occurred in 5 patients. A second total synovectomy was performed in 4 patients. Radiotherapy was used for the remaining one patient. Two patients were operated three times. During the follow-up, TKR was performed in 7 of the 19 patients. None of the patients developed infection and hemarthrosis requiring puncture nor required amputation or arthrodesis. Three patients had a postoperative knee joint stiffness of 10 to 25 degrees. The patients were evaluated according to the Knee Society Score and 8 (42.2%) had perfect, 9 (47.3%) good and 2 (10.5%) bad results. CONCLUSION: PVNS is a disease with a high risk of recurrence. No individual or combined treatment method can offer a definitive solution. Open or arthroscopic radical synovectomy is still considered as the gold standard. If necessary, adjuvant intraarticular or extraarticular radiotherapy can be added to the treatment.

Arthroscopic treatment of localized pigmented villonodular synovitis: long-term functional results.

Pigmented villonodular synovitis (PVNS) is a proliferative disorder that may lead to joint destruction and activity limitation. We conducted a retrospective study to determine the long-term results of localized PVNS (LPVNS) treated with arthroscopic excision, specifically with respect to postoperative activity level and symptom resolution. We reviewed the cases of 11 patients who had been treated with arthroscopic excision and partial synovectomy of LPVNS and been followed up for a mean of 112 months. Preoperative and postoperative Ogilvie-Harris scores, Tegner activity level scores, and UCLA activity level scores were calculated to determine disease-specific and general functional outcomes, respectively. We noted 2 cases in which posteromedial lesions recurred, moderate resolution of preoperative symptoms in most cases, and 2 cases in which the patient developed secondary osteoarthritis requiring surgical intervention. Arthroscopic excision of LPVNS can improve symptoms with a return to preoperative activity levels, but patients may develop secondary osteoarthritis after treatment, as noted in long-term follow-up.

Postoperative management of pigmented villonodular synovitis in a single subject.

STUDY DESIGN: Case report. BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare, benign disorder characterized by idiopathic proliferation affecting the synovium of joints, tendon sheaths, and bursae. Diagnosing PVNS in the knee is difficult because the clinical presentation and symptoms mimic those of more common disorders at the joint, such as internal derangements or arthritis. Operative treatment of PVNS typically consists of arthroscopic or open synovectomy, but no reports of postoperative rehabilitation exist. CASE DESCRIPTION: This case describes the postoperative rehabilitation of a 46-year-old female who had left knee surgery secondary to PVNS. Rehabilitation consisted of combined manual therapy, exercise, and gait training to improve function and gait, and cognitive-behavioral techniques to improve self-efficacy. OUTCOMES: All impairments improved in 2.5 months of physical therapy to normal, and the patient estimated 80% to 90% return to function. DISCUSSION: This patient obtained excellent outcomes in 2.5 months of physical therapy following surgery for PVNS. Although no firm conclusions can be drawn from a case report, this patient responded well to a biopsychosocial approach that combined physical therapy with cognitive-behavioral techniques. LEVEL OF EVIDENCE: Therapy, level 4.

Pigmented villonodular synovitis originating from the lumbar facet joint: a case report.

The authors successfully treated a rare case of pigmented villonodular synovitis (PVNS) that originated from the lumbar facet joint (L4-5). A 43-year-old man presented with a complaint of left severe sciatica causing difficulty in walking. Magnetic resonance imaging (MRI) demonstrated an extradural mass on the left side at L4 and the mass compressed the dural tube and was continuous with the left L4-5 facet joint. A computed tomography myelogram revealed an extradural defect of contrast medium at the L4 level and an erosion of the L4 lamina. A total synovectomy with unilateral osteoplastic laminectomy was performed. The histological findings were a diagnosis of PVNS. The patient's symptoms resolved completely and the MRI at postoperative 3 years demonstrated no recurrence of PVNS. It is important to totally remove the synovium, which is the origin of PVNS in order to prevent the recurrence. We think that our procedure is reasonable and adequate for lumbar PVNS.

Pigmented villonodular synovitis: an uncommon presentation of anterior hip pain.

Pigmented villonodular synovitis (PVNS) is a rare, benign, idiopathic proliferative disorder of the synovium that results in villous or nodular formation in joints, tendon sheaths, and bursae. The disease can be localized or diffuse. Its estimated prevalence is 1.8 cases per million in the United States. Large joints, such as the knee and hip, are commonly affected. Patients with this condition typically present with symptoms of mild discomfort and associated stiffness of the involved joint; however, the spectrum of presentations is broad. We present a case of an otherwise healthy 40-yr-old man who presented for evaluation of stiffness and pain in the anterior hip. His initial presentation, work-up, and course will be discussed, along with a brief review of the literature.

Apoptosis resistance in pigmented villonodular synovitis.

OBJECTIVE: Pigmented villonodular synovitis (PVNS) is a proliferative lesion originating from synovial tissue with a locally aggressive behaviour. We analysed the pathogenetic role of apoptosis resistance for sustained cell proliferation in PVNS. METHODS: The expression of bcl-2, p53 and Ki-67 was examined in 80 cases of PVNS using immunohistochemistry. In 43 of these cases, DNA content and distribution of cell-cycle phases were investigated by flow cytometry. Additionally, 10 cases of PVNS were analysed by multi-parametric flow cytometry for expression of p53, caspase3, and bcl-2 and by TUNEL to detect DNA fragmentation. RESULTS: No apoptotic cell fractions were detected in any investigated cases. Expression of bcl-2 was found in 84% of cases (up to 6.5% of cells) and was significantly associated with DNA-fragmentation observed by TUNEL (p=0.037). Orthologous p53 expression was observed in 37% of cases. The level of p53 expression correlated with the proliferative activity and the expression of both caspase3 (p=0.017) and bcl-2 (p=0.0013). (No statistically significant correlations between expression of bcl-2, p53, caspase3, DNA fragmentation or proliferative index and age, sex of patients, disease recurrence, growth pattern or size of lesion were found). CONCLUSION: Apoptosis resistance is a critical event in the progression of PVNS and may contribute to the survival of the proliferating synovial cells in PVNS and to the permanent slow progression of these lesions.

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in pigmented villonodular synovitis suggests their potential role for joint destruction.

OBJECTIVE: Pigmented villonodular synovitis (PVNS) is an uncommon idiopathic, proliferative synovial disease. Since matrix metalloproteinases (MMP) are assumed to play an important role in the pathogenesis of PVNS, we examined the expression and activity of MMP and tissue inhibitor of metalloproteinases (TIMP) in PVNS. METHODS: Synovial tissue samples were obtained from 10 patients with PVNS (knee 8, ankle 2) and 4 patients each with rheumatoid arthritis (RA) or osteoarthritis (OA) for comparison. Protein deposition and mRNA expression were determined by conventional immunohistochemical studies and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Gelatin zymography was performed for detection of gelatin-degrading activity. The quantity of MMP and TIMP was measured by ELISA. RESULTS: Intense immunostaining for MMP-1 was detected in both the multinucleated giant cells and mononuclear cells, whereas TIMP-1 was weakly positive. MMP-9 immunostained predominantly in the multinucleated cells, whereas other MMP and TIMP were weakly detected. RT-PCR analysis showed that mRNA expression of MMP-9 was stimulated in PVNS, whereas MMP-2 mRNA was not, compared to RA or OA. The gelatin zymogram indicated protease activities predominantly at 92 kDa and 67 kDa. In accord with the immunostaining results, the amount of MMP-1 and MMP-9 protein was significantly higher than that of TIMP-1 and MMP-2, respectively. CONCLUSION: We characterized the expression and activity of MMP in PVNS and observed that PVNS tissues predominantly produce MMP-1 and MMP-9. Given that PVNS occasionally induces joint destruction, stimulated expression of MMP-1 and MMP-9 may contribute to the invasive activity and the bone and cartilage loss in PVNS.