Developmental regulation of biglycan expression in muscle and tendon

Lechner, Beatrice E.; Lim, Jae Hwan; Mercado, Mary Lynn T.; Fallon, Justin R.

doi:10.1002/mus.20596

Cited by 36 publications

(27 citation statements)

References 36 publications

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“…Biglycan is prominent in murine tendon development, where it is expressed during embryonic development and is colocalized with collagen type VI (Lechner et al, 2006). In bovine tendon, biglycan is expressed throughout embryonic development and early postnatal development within all regions of the tendon (Vogel and Trotter, 1987;Evanko and Vogel, 1990).…”

Section: Biglycanmentioning

confidence: 99%

Collagen fibrillogenesis in tendon development: Current models and regulation of fibril assembly

Banos

Thomas

Kuo

2008

Birth Defects Research Pt C

116

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Tendons are collagen-based fibrous tissues that connect and transmit forces from muscle to bone. These tissues, which are high in collagen type I content, have been studied extensively to understand collagen fibrillogenesis. Although the mechanisms have not been fully elucidated, our understanding has continued to progress. Here, we review two prevailing models of collagen fibrillogenesis and discuss the regulation of the process by candidate cellular and extracellular matrix molecules. Although numerous molecules have been implicated in the regulation of collagen fibrillogenesis, we focus on those that have been suggested to be particularly relevant to collagen type I fibril formation during tendon development, including members of the collagen and small leucine-rich proteoglycan families, as well as other molecules, including scleraxis, cartilage oligomeric matrix protein, and cytoskeletal proteins.

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Section: Biglycanmentioning

confidence: 99%

Collagen fibrillogenesis in tendon development: Current models and regulation of fibril assembly

Banos

Thomas

Kuo

2008

Birth Defects Research Pt C

116

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“…Proteoglycans and their constituent GAGs can influence many important physiological processes in tendon, including ion transport, water retention, the diffusion of nutrients, mediating cell-matrix interactions, resistance of compression and sequestration of growth factors and enzymes in the matrix [43,116]. Animal studies demonstrate biglycan may serve both a structural [109] and a signaling role [77] in developing tendon and biglycan and collagen VI are coexpressed in tendon development [61]. It is possible the presence of tendon fibrocartilage proteoglycan/glycosaminoglycan in normal supraspinatus is part of a normal functional adaptation to mechanical forces in tendon [91].…”

Section: Extracellular Matrix (Ecm)mentioning

confidence: 99%

The Basic Science of Tendinopathy

Murrell

2008

Clinical Orthopaedics &Amp; Related Research

314

254

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Tendinopathy is a common clinical problem with athletes and in many occupational settings. Tendinopathy can occur in any tendon, often near its insertion or enthesis where there is an area of stress concentration, and is directly related to the volume of repetitive load to which the tendon is exposed. Recent studies indicate tendinopathy is more likely to occur in situations that increase the ''dose'' of load to the tendon enthesis -including increased activity, weight, advancing age, and genetic factors. The cells in tendinopathic tendon are rounder, more numerous, and show evidence of oxidative damage and more apoptosis. These cells also produce a matrix that is thicker and weaker with more water, more immature and cartilage-like matrix proteins, and less organization. There is now evidence of a population of regenerating stem cells within tendon. These studies suggest prevention of tendinopathy should be directed at reducing the volume of repetitive loads to below that which induces oxidative-induced apoptosis and cartilage-like genes. The management strategies might involve agents or cells that induce tendon stem cell proliferation, repair and restoration of matrix integrity.

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“…In both humans and mice, biglycan is most highly expressed in immature and regenerating muscle (11,12). Biglycan is a component of the DAPC, where it binds to α-dystroglycan (13) and α-and γ-sarcoglycan (14).…”

mentioning

confidence: 99%

Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice

Amenta¹,

Yilmaz

Bogdanovich

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

136

103

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Duchenne muscular dystrophy (DMD) is caused by mutations in dystrophin and the subsequent disruption of the dystrophin-associated protein complex (DAPC). Utrophin is a dystrophin homolog expressed at high levels in developing muscle that is an attractive target for DMD therapy. Here we show that the extracellular matrix protein biglycan regulates utrophin expression in immature muscle and that recombinant human biglycan (rhBGN) increases utrophin expression in cultured myotubes. Systemically delivered rhBGN upregulates utrophin at the sarcolemma and reduces muscle pathology in the mdx mouse model of DMD. RhBGN treatment also improves muscle function as judged by reduced susceptibility to eccentric contraction-induced injury. Utrophin is required for the rhBGN therapeutic effect. Several lines of evidence indicate that biglycan acts by recruiting utrophin protein to the muscle membrane. RhBGN is well tolerated in animals dosed for as long as 3 months. We propose that rhBGN could be a therapy for DMD.biotherapeutics | protein therapeutics D uchenne muscular dystrophy (DMD) is a hereditary disease that affects ∼1:3,500 boys, the majority of whom will die by their midtwenties (1). DMD is caused by mutations in dystrophin that result in the faulty assembly and function of an ensemble of structural and signaling molecules at the muscle cell surface termed the dystrophin-associated protein complex (DAPC) (2-4). There are currently no treatments that target the primary pathology of DMD.One attractive therapeutic approach for DMD is the stabilization of the muscle cell membrane through up-regulation of utrophin, a dystrophin homolog. Transgenic overexpression of utrophin rescues dystrophic pathology and restores function in the dystrophin-deficient mdx mouse (5-7). In mature muscle, utrophin expression is restricted to the neuromuscular and myotendinous junctions. However, utrophin is expressed over the entire myofiber in developing and regenerating muscle (8-10). These observations raise the possibility that marshalling pathways that normally regulate utrophin expression in developing muscle could be a productive approach for developing DMD treatments.The extracellular matrix protein biglycan plays an important role in developing muscle. In both humans and mice, biglycan is most highly expressed in immature and regenerating muscle (11,12). Biglycan is a component of the DAPC, where it binds to α-dystroglycan (13) and α-and γ-sarcoglycan (14). Biglycan regulates the expression of the sarcoglycans as well as dystrobrevins, syntrophins, and nNOS, particularly in immature muscle. Finally, biglycan is important for timely muscle regeneration (11).Locally delivered recombinant human biglycan (rhBGN) incorporates into the extracellular matrix of bgn −/o muscle where it persists for at least 2 wk and rescues the expression of several DAPC components (15). These results raise the possibility that rhBGN might enhance function in muscle that lacks dystrophin. Here we show that utrophin is down-regulated in immature biglycan null (...

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Developmental regulation of biglycan expression in muscle and tendon

Cited by 36 publications

References 36 publications

Collagen fibrillogenesis in tendon development: Current models and regulation of fibril assembly

Collagen fibrillogenesis in tendon development: Current models and regulation of fibril assembly

The Basic Science of Tendinopathy

Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice

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