Linda J. Sandell

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The reaction patterns of chondrocytes in osteoarthritis can be summarized in five categories: (1) proliferation and cell death (apoptosis); changes in (2) synthetic activity and (3) degradation; (4) phenotypic modulation of the articular chondrocytes; and (5) formation of osteophytes. In osteoarthritis, the primary responses are reinitiation of synthesis of(More)
OBJECTIVE To provide a more complete picture of the effect of interleukin-1 beta (IL-1beta) on adult human articular chondrocyte gene expression, in contrast to the candidate gene approach. DESIGN Chondrocytes from human knee cartilage were cultured in medium containing IL-1beta. Changes in gene expression were analyzed by microarray and reverse(More)
Osteoarthritis (OA) has a considerable hereditary component and is considered to be a polygenic disease. Data derived from genetic analyses and genome-wide screening of individuals with this disease have revealed a surprising trend: genes associated with OA tend to be related to the process of synovial joint development. Mutations in these genes might(More)
Platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1), two growth-regulatory peptides with opposite effects on arterial smooth muscle cell (ASMC) proliferation, were examined for their influence on the synthesis of two small chondroitin sulfate/dermatan sulfate proteoglycans (CS/DS PGs) called biglycan and decorin.(More)
Platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1) increase [35S]sulfate incorporation into proteoglycan (PG) by monkey arterial smooth muscle cells but have opposite effects on cell proliferation. The combination of these two growth regulatory peptides has an additive effect on PG synthesis but no effects on cell(More)
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of(More)
A cDNA encoding a novel protein has been previously isolated from two independent sources: melanoma cell cultures and chondrocytes. The protein from human melanoma cell lines and tumors is called melanoma inhibitory activity (MIA) (Blesch et al. [1994] Cancer Res. 54:5695-5701) and the protein from primary bovine chondrocytes and cartilaginous tissues is(More)
Type II collagen is a major component of cartilage providing structural integrity to the tissue. Type II procollagen can be expressed in two forms by differential splicing of the primary gene transcript. The two mRNAs either include (type IIA) or exclude (type IIB) an exon (exon 2) encoding the major portion of the amino (NH2)-propeptide (Ryan, M. C., and(More)
BACKGROUND Destruction of cartilage in osteoarthritis is a direct effect of an imbalance between catabolic and anabolic activities in the tissue. While a great deal is known about catabolism, we sought to determine the biochemical basis of the anabolic activity. METHODS Cartilage was isolated from normal and osteoarthritic patients and subjected to both(More)
The transcription factor Sox9 is capable of enhancing type II collagen gene expression and may play a crucial role in chondrogenesis. To determine whether Sox9 is an inducer of the chondrocyte phenotype, we investigated the role of Sox9 in transcription of another cartilage gene encoding the cartilage-derived retinoic acid-sensitive protein (CD-RAP). CD-RAP(More)