Objective. To explore the role of meniscal tears and meniscal malposition as risk factors for subsequent cartilage loss in subjects with symptomatic osteoarthritis (OA).Methods. Study subjects were patients with symptomatic knee OA from the Boston Osteoarthritis of the Knee Study. Baseline assessments included knee magnetic resonance imaging (MRI) with followup MRI at 15 and 30 months. Cartilage and meniscal damage were scored on MRI in the medial and lateral tibiofemoral joints using the semiquantitative whole-organ magnetic resonance imaging score. Tibiofemoral cartilage was scored on MR images of all 5 plates of each tibiofemoral joint, and the meniscal position was measured using eFilm Workstation software. A proportional odds logistic regression model with generalized estimating equations was used to assess the effect of each predictor (meniscal position factor and meniscal damage as dichotomous predictors in each model) on cartilage loss in each of the 5 plates within a compartment. Models were adjusted for age, body mass index (BMI), tibial width, and sex.Results. We assessed 257 subjects whose mean ؎ SD age was 66.6 ؎ 9.2 years and BMI was 31.5 ؎ 5.7 kg/m 2 ; 42% of subjects were female, and 77% of knees had a Kellgren/Lawrence radiographic severity grade >2. In the medial tibiofemoral joint, each measure of meniscal malposition was associated with an increased risk of cartilage loss. There was also a strong association between meniscal damage and cartilage loss. Since meniscal coverage and meniscal height diminished with subluxation, less coverage and reduced height also increased the risk of cartilage loss.Conclusion. This study highlights the importance of an intact and functioning meniscus in patients with symptomatic knee OA, since the findings demonstrate that loss of this function has important consequences for cartilage loss.Cartilage loss in knee osteoarthritis (OA) is a multifactorial process that is influenced by systemic risk factors such as age, sex, and obesity and by local mechanical factors such as alignment and injury. One of the important local mechanical factors is the integrity and function of the meniscus. The meniscus has many functions in the knee, including load bearing, shock absorption, stability enhancement, and lubrication (1,2). Knee OA after meniscectomy is traditionally considered a result of the joint injury that leads to the meniscectomy in the first instance, and the increased contact stress in the cartilage due to the loss of meniscal tissue (3-8). Meniscectomy is often accompanied by the onset of OA because of the high focal stresses imposed on articular cartilage and subchondral bone subsequent to excision of the meniscus. Studies of meniscectomy affirm the importance of loss of meniscal function as a risk factor for subsequent knee OA (9).Although meniscectomy appears to be an important risk factor for OA, we know little about the effect of meniscal tears and meniscal extrusion or subluxation on cartilage loss in knees with preexisting OA. Results from a cross-sectio...

No abstract

The involvement of Mts1(S100A4), a small Ca 2+ -binding protein in tumor progression and metastasis had been demonstrated. However, the mechanism by which mts1(S100A4) promoted metastasis had not been identi®ed. Here we demonstrated that Mts1(S100A4) had signi®cant stimulatory eect on the angiogenesis. We detected high incidence of hemangiomas ± benign tumors of vascular origin in aged transgenic mice ubiquitously expressing the mts1(S100A4) gene. Furthermore, the serum level of the Mts1(S100A4) protein increased with ageing. Tumors developed in Mts1-transgenic mice revealed an enhanced vascular density. We showed that an oligomeric, but not a dimeric form of the Mts1(S100A4) protein was capable of enhancing the endothelial cell motility in vitro and stimulate the corneal neovascularization in vivo. An oligomeric fraction of the protein was detected in the conditioned media as well as in human serum. The data obtained allowed us to conclude that mts1(S100A4) might induce tumor progression via stimulation of angiogenesis. Oncogene (2001) 20, 4685 ± 4695.

The gene mtsl, which is expressed specifically in metastatic cells, was isolated by molecular cloning coupled with differential DNA reassociation. Transcription of mtsl was found not only in tumor cells, but also in normal cells; homologous RNA was detected only in spleen, thymus, bone marrow, and blood lymphocytes. DNA sequencing of mtsl revealed an open reading frame containing information for a peptide of 101 amino acids, and the amino acid sequence suggested that the mtsl protein was identical to the previously isolated Ca2+-binding mouse protein (Jackson-Grusby et al. 1987; Goto et al. 1988). Thus, the mtsl protein is a member of the calcium-modulated protein family, and our data indicate that mtsl is involved in regulating the metastatic behavior of tumor cells.

Neuronal differentiation and axonal growth are controlled by a variety of factors including neurotrophic factors, extracellular matrix components, and cell adhesion molecules. Here we describe a novel and very efficient neuritogenic factor, the metastasis-related Mts1 protein, belonging to the S100 protein family. The oligomeric but not the dimeric form of Mts1 strongly induces differentiation of cultured hippocampal neurons. A mutant with a single Y75F amino acid substitution, which stabilizes the dimeric form of Mts1, is unable to promote neurite extension. Disulfide bonds do not play an essential role in the Mts1 neuritogenic activity. Mts1-stimulated neurite outgrowth involves activation of phospholipase C and protein kinase C, depends on the intracellular level of Ca 2؉ , and requires activation of the extracellular signal-regulated kinases (ERKs) 1 and 2.