Lessons from rare diseases of cartilage and bone

Gallagher, James A.; Ranganath, L.; Boyde, A.

doi:10.1016/j.coph.2015.04.002

Cited by 20 publications

(14 citation statements)

References 63 publications

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“…These pieces of evidence imply that EPM formation could be favored under abnormal conditions that upset local tissue homeostasis. Ectopic mineralization could conceivably be triggered by a decrease in local proteoglycan content that allows mineralizing ions more access to collagen fibers (as proposed for some mammalian cartilage diseases; Gallagher et al, 2015;Kalya & Rosenthal, 2005;Kemp & Westrin, 1979), a change in chondrocyte health, or a decrease in pH below the neutral pH of elasmobranch body sera (see citations in Supplementary Table 4: Dean et al, 2015) since the calcium phosphate mineral suggested by our data (brushite) precipitates in acidic solutions (pH ~5; Galea et al, 2013;Shellis et al, 1997).…”

Section: Epm Etiologymentioning

confidence: 79%

“…11C-D) (Boyde et al, 2011(Boyde et al, , 2014). It appears that HDMPs form in the cracks in the subchondral plate that follow abnormal cartilage matrix stiffening, which can be caused by age-or disease-related modifications of the proteoglycans that typically protect collagens and inhibit mineralization of cartilage (Gallagher et al, 2015). Like EPMs, HDMPs exhibit comparatively high mineral density and grow endophytically into uncalcified cartilage.…”

Section: Figure 11 Skeletal Pathologies In Vertebrates (Cartilaginoumentioning

confidence: 99%

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Ultrastructural, material and crystallographic description of endophytic masses – A possible damage response in shark and ray tessellated calcified cartilage

Seidel

Blumer

Zaslansky

et al. 2017

Journal of Structural Biology

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The cartilaginous endoskeletons of elasmobranchs (sharks and rays) are reinforced superficially by minute, mineralized tiles, called tesserae. Unlike the bony skeletons of other vertebrates, elasmobranch skeletons have limited healing capability and their tissues' mechanisms for avoiding damage or managing it when it does occur are largely unknown. Here we describe an aberrant type of mineralized elasmobranch skeletal tissue called endophytic masses (EPMs), which grow into the uncalcified cartilage of the skeleton, but exhibit a strikingly different morphology compared to tesserae and other elasmobranch calcified tissues. We use materials and biological tissue characterization techniques, including computed tomography, electron and light microscopy, X-ray and Raman spectroscopy and histology to characterize the morphology, ultrastructure and chemical composition of tesserae-associated EPMs in different elasmobranch species. EPMs appear to develop between and in intimate association with tesserae, but lack the lines of periodic growth and varying mineral density characteristic of tesserae. EPMs are mineral-dominated (high mineral and low organic content), comprised of birefringent bundles of large calcium phosphate crystals (likely brushite) aligned end to end in long strings. Both tesserae and EPMs appear to develop in a type-2 collagen-based matrix, but in contrast to tesserae, all chondrocytes embedded or in contact with EPMs are dead and mineralized. The differences outlined between EPMs and tesserae demonstrate them to be distinct tissues. We discuss several possible reasons for EPM development, including tissue reinforcement, repair, and disruptions of mineralization processes, within the context of elasmobranch skeletal biology as well as damage responses of other vertebrate mineralized tissues.

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Section: Epm Etiologymentioning

confidence: 79%

Section: Figure 11 Skeletal Pathologies In Vertebrates (Cartilaginoumentioning

confidence: 99%

Ultrastructural, material and crystallographic description of endophytic masses – A possible damage response in shark and ray tessellated calcified cartilage

Seidel

Blumer

Zaslansky

et al. 2017

Journal of Structural Biology

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“…There is also the opportunity when studying rare musculoskeletal diseases, such as alkaptonuria (AKU), for researchers to determine whether treatments developed specifically for these can facilitate the development of new therapies for the more common disorders. There may also be common pathways in disease progression, which may help understanding of how and why individuals develop musculoskeletal problems [138].…”

Section: Current Research Approaches For Musculoskeletal Diseasesmentioning

confidence: 99%

Strategies for optimising musculoskeletal health in the 21st century

Lewis

Álvarez

Rayman

et al. 2019

BMC Musculoskelet Disord

130

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We live in a world with an ever-increasing ageing population. Studying healthy ageing and reducing the socioeconomic impact of age-related diseases is a key research priority for the industrialised and developing countries, along with a better mechanistic understanding of the physiology and pathophysiology of ageing that occurs in a number of age-related musculoskeletal disorders. Arthritis and musculoskeletal disorders constitute a major cause of disability and morbidity globally and result in enormous costs for our health and social-care systems. By gaining a better understanding of healthy musculoskeletal ageing and the risk factors associated with premature ageing and senescence, we can provide better care and develop new and better-targeted therapies for common musculoskeletal disorders. This review is the outcome of a two-day multidisciplinary, international workshop sponsored by the Institute of Advanced Studies entitled "Musculoskeletal Health in the 21st Century" and held at the University of Surrey from 30th June-1st July 2015. The aim of this narrative review is to summarise current knowledge of musculoskeletal health, ageing and disease and highlight strategies for prevention and reducing the impact of common musculoskeletal diseases.

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“…Those that do possess what would be described as lesions appear ochronotic and are typified by mechanical damage from contact between brittle cartilage on opposing surfaces, rather than by the enzymatic degradation and lesions typically observed with OA. Because the presence of pigment initially protects cartilage from overt breakdown, early radiographs appear normal, while cartilage is pigmenting/pigmented [34]. Only when mechanical trauma dislodges cartilage may radiological changes be observed; therefore, other diagnostic measures for assessing the state of joints of individuals with AKU, particularly during early joint pathological stages, may be more appropriate.…”

Section: Discussionmentioning

confidence: 99%

Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing

et al. 2016

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Objective. Alkaptonuria (AKU) is a rare autosomal recessive disease resulting from a single enzyme deficiency in tyrosine metabolism. As a result, homogentisic acid cannot be metabolized, causing systemic increases. Over time, homogentisic acid polymerizes and deposits in collagenous tissues, leading to ochronosis. Typically, this occurs in joint cartilages, leading to an early onset, rapidly progressing osteoarthropathy. The aim of this study was to examine tissue turnover in cartilage affected by ochronosis and its role in disease initiation and progression.Methods. With informed patient consent, hip and knee cartilages were obtained at surgery for arthropathy due to AKU (n = 6; 2 knees/4 hips) and OA (n = 12; 5 knees/7 hips); healthy non-arthritic (non-OA n = 6; 1 knee/5 hips) cartilages were obtained as waste from trauma surgery. We measured cartilage concentrations (normalized to dry weight) of racemized aspartate, GAG, COMP and deamidated COMP (D-COMP). Unpaired AKU, OA and non-OA samples were compared by non-parametric MannWhitney U test.Results. Despite more extractable total protein being obtained from AKU cartilage than from OA or non-OA cartilage, there was significantly less extractable GAG, COMP and D-COMP in AKU samples compared with OA and non-OA comparators. Racemized Asx (aspartate and asparagine) was significantly enriched in AKU cartilage compared with in OA cartilage.Conclusions. These novel data represent the first examination of cartilage matrix components in a sample of patients with AKU, representing almost 10% of the known UK alkaptonuric population. Compared with OA and non-OA, AKU cartilage demonstrates a very low turnover state and has low levels of extractable matrix proteins.

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Lessons from rare diseases of cartilage and bone

Cited by 20 publications

References 63 publications

Ultrastructural, material and crystallographic description of endophytic masses – A possible damage response in shark and ray tessellated calcified cartilage

Ultrastructural, material and crystallographic description of endophytic masses – A possible damage response in shark and ray tessellated calcified cartilage

Strategies for optimising musculoskeletal health in the 21st century

Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing

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