Hyaluronan synthesis and degradation in cartilage and bone

Bastow, Edward; Byers, Sharon; Golub, Suzanne B.; Clarkin, Claire E.; Pitsillides, Andrew A.; Fosang, Amanda J.

doi:10.1007/s00018-007-7360-z

Cited by 174 publications

(114 citation statements)

References 233 publications

(194 reference statements)

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“…Aggrecan forms large aggregates, which give to cartilage its unique gel-like properties and its resistance to deformation. The central component of these aggregates is a long molecule of hyaluronan (Bastow et al 2008). Hyaluronan is the only extracellular oligosaccharide that is not covalently linked to a protein, as it is bound to aggrecan in a noncovalent fashion.…”

Section: Molecular Mechanisms Underlying Joint Formationmentioning

confidence: 99%

MicroRNA-140 and the silencing of osteoarthritis

Araldi¹,

Schipani²

2010

Genes Dev.

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MicroRNAs (miRNAs) have emerged as important modulators in development, tissue homeostasis, and diseases. In this issue of Genes & Development, Miyaki and colleagues (pp. 1173–1185) report that miR-140 is involved in the pathogenesis of osteoarthritis by regulating, at least in part, ADAMTS5. Moreover, mice lacking miR-140 are dwarf as a consequence of impaired chondrocyte proliferation. This study is the first in vivo demonstration that miR-140 has a critical and nonredundant role in cartilage development and homeostasis.

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Section: Molecular Mechanisms Underlying Joint Formationmentioning

confidence: 99%

MicroRNA-140 and the silencing of osteoarthritis

Araldi¹,

Schipani²

2010

Genes Dev.

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“…ECM turnover remains at relatively low rates and resists proliferation and differentiation. During degeneration, type X collagen (COLX) and MMP13 are overexpressed in fibrocartilage with lower amounts of proteoglycans, decreased UF zone, and expanded CF zone (19)(20)(21)(22). Blood vessels and bony defects are also often present, and the blood vessels may pass between the tendon/ligament and the bone marrow (23).…”

Section: Introductionmentioning

confidence: 99%

Aberrant TGF-β activation in bone tendon insertion induces enthesopathy-like disease

Wang¹,

Xie²,

Crane³

et al. 2018

Journal of Clinical Investigation

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and systemically in spondyloarthropathy patients with enthesopathy (37,38). In this study, we determined the role of TGF-β in Achilles tendon enthesopathy using 3 different mouse models. We found that the changes of calcaneal bone microstructure and composition were associated with the onset of Achilles tendon enthesopathy. Inhibition of TGF-β activity, using either a TGF-β-neutralizing antibody (1D11) or a conditional knockout mouse model, attenuated calcaneal and fibrocartilage pathological changes. ResultsUpregulated TGF-β activities in posterior calcaneal tuberosity in Achilles tendon enthesopathy mouse models. To examine the changes at the disease has drawn increasing attention in recent years. During tissue injury or remodeling, TGF-β is activated to recruit stem/ progenitor cells to maintain tissue homeostasis (27)(28)(29)(30)(31). We have previously shown that TGF-β is released from the bone matrix and activated during osteoclastic bone resorption (31). Active TGF-β induces mesenchymal stromal stem cell (MSC) migration to the bone-resorptive pits for new bone formation (31). However, excessive active TGF-β leads to uncoupled bone remodeling, contributing to the pathogenesis of rare genetic skeletal diseases such as Camurati-Engelmann disease (CED), osteogenesis imperfecta, and more common musculoskeletal disorders, such as osteoarthritis (31-36). High levels of TGF-β have been observed locally lower in relation to sham-operated controls ( Figure 1B). Moreover, a dramatically higher trabecular pattern factor (Tb.Pf), a quantitative parameter of the connectiveness and microarchitecture of trabecular bone (40), was noted in the SMTS mice compared with sham-operated controls, indicating uncoupled bone remodeling ( Figure 1B). Evident bony projections at the PCT were present in 4 of 10 mice 8 weeks after SMTS ( Figure 1A). The BV/TV, Tb.N, and Tb.Th of vertebral bodies were not significantly changed in the SMTS group compared with controls at week 8 (Supplemental Figure 2). Tartrate-resistant acid phosphatase (TRAP) staining showed that the osteoclast surface per bone surface (OCS/BS) increased in PCT trabecular bone 1 and 2 weeks after surgery and was back to normal levels on week 4 after surgery (Figure 1, C and D) while leaving large bone marrow cavities ( Figure 1C). A significantly higher active TGF-β concentration in serum was seen in the SMTS mice relative to sham-operated mice from 1 to 8 weeks after onset of enthesopathy, we generated these 2 models based on prior theories that enthesopathy results from unbalanced mechanical loading (2, 39). The first model we generated decreased mechanical load by partially transecting Achilles tendons in the middle of tendon body in 3-month-old male mice, termed semi-Achilles tendon transection (SMTS) (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/ JCI96186DS1). The bone volume over total tissue volume (BV/ TV) in the posterior calcaneal tuberosity (PCT), the site of Achilles tendon attachment to calcane...

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“…In the joints, synovial cells produce HA, a component of synovial fluid GAG, whereas chondrocytes produce chondroitin (15)(16)(17)(18)(19). Thus, it is reasonable to speculate that GlcN may affect GAG production by synovial cells and chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Effects of glucosamine derivatives and uronic acids on the production of glycosaminoglycans by human synovial cells and chondrocytes

Nagaoka¹

2011

Int J Mol Med

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Abstract. Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. However, its chondroprotective action on the joint is poorly understood. In this study, to elucidate the chondroprotective action of GlcN, we examined the effects of GlcN-derivatives (GlcN and N-acetyl-d-glucosamine) and uronic acids (d-glucuronic acid and d-galacturonic acid) (0.1-1 mM) on the production of glycosaminoglycans (GAG), such as hyaluronic acid (HA), keratan sulfate and sulfated GAG by human synovial cells and chondrocytes. The results indicate that among GlcN-derivatives and uronic acids, GlcN but not N-acetyld-glucosamine, d-glucuronic acid and d-galacturonic acid induce the production of HA by synovial cells and chondrocytes at >0.25 and >0.1 mM (p<0.05), respectively, and the production levels are much higher (>10-fold) in synovial cells compared to chondrocytes. In contrast, neither N-acetyld-glucosamine, d-glucuronic acid nor d-galacturonic acid affected the production of keratan sulfate and sulfated GAG by these cells. Moreover, the experiments with 3 H-labeled GlcN indicated that GlcN can be incorporated and utilized for the production of GAG (including HA) by synovial cells and chondrocytes. In addition, GlcN (1 mM) up-regulates the expression of HA-synthesizing enzymes (hyaluronan synthases) in synovial cells and chondrocytes. Together these observations indicate that GlcN may exhibit chondroprotective action on joint diseases such as OA by modulating the expression of HA-synthesizing enzymes and inducing the production of HA (a major component of GAG contained in synovial fluid) especially by synovial cells. IntroductionOsteoarthritis (OA) is the most common joint disorder with an immense socioeconomic impact. OA is characterized by qualitative and quantitative changes in the architecture and composition of all the joint structures (1,2). An altered imbalance among the biosynthesis and degradation of matrix components leads to a progressive destruction of the tissue (3). currently, several treatments are available for OA ranging from conservative treatments to surgical extremes. conservative measures involve lifestyle modifications, physical therapy and pharmacological treatment with non-steroidal antiinflammatory drugs (NSAIDs) and intra-articular injection of hyaluronic acid (HA) (4). Treatments for early OA are primarily based on symptomatic relief, whereas irreversible joint disability in advanced OA usually requires surgical intervention to relieve pain and improve joint function (5). However, current treatments are mostly targeting the OA symptoms and not addressing the destructed structure of articular cartilage in OA.Glucosamine (GlcN), a naturally occurring amino monosaccharide, is present in the connective and cartilage tissues as a component of glycosaminoglycans (GAG). GlcN contributes to the maintainance of the strength, flexibility and elasticity of these tissues. Thus, GlcN has been widely used to treat OA for more than two decades in humans (6-9). Several short-and long-term clinica...

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Hyaluronan synthesis and degradation in cartilage and bone

Cited by 174 publications

References 233 publications

MicroRNA-140 and the silencing of osteoarthritis

MicroRNA-140 and the silencing of osteoarthritis

Aberrant TGF-β activation in bone tendon insertion induces enthesopathy-like disease

Effects of glucosamine derivatives and uronic acids on the production of glycosaminoglycans by human synovial cells and chondrocytes

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