Asporin-deficient mice have tougher skin and altered skin glycosaminoglycan content and structure

Maccarana, Marco; Svensson, René B.; Knutsson, Anki; Giannopoulos, Antonis; Pelkonen, Mea; Weis, Mary Ann; Eyre, David R.; Warman, Matthew L.; Kalamajski, Sebastian

doi:10.1371/journal.pone.0184028

Cited by 12 publications

(9 citation statements)

References 44 publications

(57 reference statements)

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“…Collagen fibrils have greater elongation at higher strain rates (Clemmer et al, 2010), and theoretically collagen could play a more important role at higher strain rates. Our study also reported asporin expression in diseased ACLs, however ASPN lacks GAG chains (Maccarana et al, 2017) usually associated with increased viscosity (Kershaw-Young et al, 2013) and therefore is unlikely to play a role in viscoelastic behaviour. Further research is needed to fully map proteoglycan and noncollagenous composition in the ACL during OA and their role in biomechanics.…”

Section: Discussionsupporting

confidence: 69%

“…The small size of the murine ACL and these inaccuracies could account for the high deviation seen in the stress-strain curves and the negative hysteresis measured. Negative hysteresis has been previously reported in human tendons (Peltonen et al, 2013;Zelik and Franz, 2017) and attributed to testing inaccuracies. However, negative hysteresis was only measured in the faster 10%/s strain rates at areas of high stress, similar to what was reported previously in the human Achilles tendon (Peltonen et al, 2013).…”

Section: Discussionmentioning

confidence: 59%

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The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics

Ramos‐Mucci

Elsheikh

Keenan

et al. 2021

Preprint

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1AbstractOsteoarthritis (OA) is a whole joint disease that affects all knee joint tissues. Ligaments, a matrix-rich connective tissue, play an important mechanical function that stabilises the knee joint and yet their role in OA is not well studied. Recent studies have shown that ligament extracellular matrix (ECM) structure is compromised in the early stages of OA, but it remains unclear how this affects ligament function and biomechanics. In this study, the aim was to investigate the structural, cellular and viscoelastic changes in the anterior cruciate ligament (ACL) in a murine non-invasive post-traumatic OA (PTOA) model. Non-invasive mechanical loading of the knee joint of C57BL/6J mice (10-week-old) was used as a PTOA model. Knee joints were analysed for joint space mineralisation and the ACLs were assessed with histology and mechanical testing. PTOA knee joints had a 33-46% increase in joint space mineralisation and PTOA knee joint ACLs exhibited ECM modifications, including collagen birefringence and COL2 and proteoglycan deposition. ECM changes were associated with cells expressing chondrogenic markers (SOX9 and RUNX2) expanding from the tibial enthesis to the ACL midbody. Viscoelastic and mechanical changes in the ACLs from PTOA knee joints included a 20-21% decrease in tangent modulus at 2MPa of stress, and a decrease strain rate sensitivity at higher strain rates and a significant increase in relaxation during stress-relaxation, but no changes to hysteresis and ultimate load to failure. These results demonstrate that ACL pathology and viscoelastic function is compromised in murine PTOA knee joints and provides further evidence of the important role of ligaments in the knee joint organ in health and disease.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 59%

The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics

Ramos‐Mucci

Elsheikh

Keenan

et al. 2021

Preprint

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“…It is reported that several PGs (HAPLN1, HAPLN2, HAPLN3, and HAPLN4) highly expressed in keloids stabilize and enhance the binding of chondroitin sulfate PG core proteins (VCAN, BCAN, AGRN, and NCAN) to hyaluronan 50 . We also found that the upregulated PGs (ACAN, OMD, and ASPN) are expressed in the skeleton and related to the mechanical toughness of skin 51‐53 . In addition, several downregulated PGs in keloids were related to the imbalance of skin mechanical properties.…”

Section: Discussionmentioning

confidence: 59%

“…50 We also found that the upregulated PGs (ACAN, OMD, and ASPN) are expressed in the skeleton and related to the mechanical toughness of skin. [51][52][53] In addition, several downregulated PGs in keloids were related to the imbalance of skin mechanical properties. For example, it has been reported that OGN can decrease the rate of collagen type 1 fibrillogenesis in vitro, 54 whereas DCN-or LUM-deficient mice display skin laxity and fragility.…”

Section: Discussionmentioning

confidence: 99%

The “Matrisome” reveals the characterization of skin keloid microenvironment

et al. 2021

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Keloids are fibroproliferative dermal tumors of unknown origin that are characterized by the overabundant accumulation of extracellular matrix (ECM) components. The mechanism of keloid formation has remained unclear because of a poor understanding of its molecular basis. In this study, the dermal ECM components of keloids were identified and the pathological features of keloid formation were characterized using large-scale quantitative proteomic analyses of decellularized keloid biomatrix scaffolds. We identified a total of 267 dermal core ECM and ECM-associated proteins that were differentially expressed between patients with keloids and healthy controls. Skin mechanical properties and biological processes including protease activity, wound healing, and adhesion were disordered in keloids. The integrated network analysis of the upregulated ECM proteins revealed multiple signaling pathways involved in these processes that may lead to keloid formation. Our findings may improve the scientific basis of keloid treatment and provide new ideas for the establishment of keloid models.

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“…ASPN has been found in dermis, perichondrium and periosteum, tendon, and eye sclera (Kou et al, 2007). ASPN-null mice exhibit an increased skin mechanical toughness due to the altered GAG composition and structure in the ECM (Maccarana et al, 2017). However, ASPN has not been studied in depth for its involvement in skin development and cutaneous wound healing.…”

Section: Asporin (Aspn)mentioning

confidence: 99%

Small Leucine-Rich Proteoglycans in Skin Wound Healing

2020

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Healing of cutaneous wounds is a complex and well-coordinated process requiring cooperation among multiple cells from different lineages and delicately orchestrated signaling transduction of a diversity of growth factors, cytokines, and extracellular matrix (ECM) at the wound site. Most skin wound healing in adults is imperfect, characterized by scar formation which results in significant functional and psychological sequelae. Thus, the reconstruction of the damaged skin to its original state is of concern to doctors and scientists. Beyond the traditional treatments such as corticosteroid injection and radiation therapy, several growth factors or cytokines-based anti-scarring products are being or have been tested in clinical trials to optimize skin wound healing. Unfortunately, all have been unsatisfactory to date. Currently, accumulating evidence suggests that the ECM not only functions as the structural component of the tissue but also actively modulates signal transduction and regulates cellular behaviors, and thus, ECM should be considered as an alternative target for wound management pharmacotherapy. Of particular interest are small leucine-rich proteoglycans (SLRPs), a group of the ECM, which exist in a wide range of connecting tissues, including the skin. This manuscript summarizes the most current knowledge of SLRPs regarding their spatial-temporal expression in the skin, as well as lessons learned from the genetically modified animal models simulating human skin pathologies. In this review, particular focus is given on the diverse roles of SLRP in skin wound healing, such as anti-inflammation, pro-angiogenesis, pro-migration, pro-contraction, and orchestrate transforming growth factor (TGF)b signal transduction, since cumulative investigations have indicated their therapeutic potential on reducing scar formation in cutaneous wounds. By conducting this review, we intend to gain insight into the potential application of SLRPs in cutaneous wound healing management which may pave the way for the development of a new generation of pharmaceuticals to benefit the patients suffering from skin wounds and their sequelae.

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Asporin-deficient mice have tougher skin and altered skin glycosaminoglycan content and structure

Cited by 12 publications

References 44 publications

The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics

The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics

The “Matrisome” reveals the characterization of skin keloid microenvironment

Small Leucine-Rich Proteoglycans in Skin Wound Healing

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