Matthew J. Silva
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View article: A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates
A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates Open
Background: Adeno-associated viral (AAV) vectors are the leading platform for gene therapy, but common delivery routes show limited spread to distal cortical structures, hence the utility of direct, intrathalamic infusions for broader tran…
View article: Proliferation of Early and Mature Osteoblasts Is Required for Bone Fracture Healing in Mice
Proliferation of Early and Mature Osteoblasts Is Required for Bone Fracture Healing in Mice Open
Fractures heal by rapid formation of mineralized callus. Essential to this process is proliferation of periosteal cells to supply bone-forming osteoblasts. To better understand the role of cell proliferation in fracture healing, we asked: …
View article: Spatial histomorphometry reveals that local peripheral nerves modulate but are not required for skeletal adaptation to applied load in mice
Spatial histomorphometry reveals that local peripheral nerves modulate but are not required for skeletal adaptation to applied load in mice Open
Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may respond to load-induced biomechanical and biochemical cues. However, their r…
View article: A proteomics approach to study mouse long bones: examining baseline differences and mechanical loading-induced bone formation in young-adult and old mice
A proteomics approach to study mouse long bones: examining baseline differences and mechanical loading-induced bone formation in young-adult and old mice Open
With aging, bone mass declines and the anabolic effects of skeletal loading diminish. While much research has focused on gene transcription, how bone ages and loses its mechanoresponsiveness at the protein level remains unclear. We develop…
View article: Spatial histomorphometry reveals that local peripheral nerves modulate but are not required for skeletal adaptation to applied load in mice
Spatial histomorphometry reveals that local peripheral nerves modulate but are not required for skeletal adaptation to applied load in mice Open
Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may respond to load-induced biomechanical and biochemical cues. However, their r…
View article: Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity
Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity Open
Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantifi…
View article: Multi‐organ phenotypes in mice lacking latent <scp>TGFβ</scp> binding protein 2 (<scp>LTBP2</scp>)
Multi‐organ phenotypes in mice lacking latent <span>TGFβ</span> binding protein 2 (<span>LTBP2</span>) Open
Background Latent TGFβ binding protein‐2 (LTBP2) is a fibrillin 1 binding component of the microfibril. LTBP2 is the only LTBP protein that does not bind any isoforms of TGFβ, although it may interfere with the function of other LTBPs or i…
View article: Multi-Scale Cortical Bone Traits Vary in Two Mouse Models of Genetic Diversity
Multi-Scale Cortical Bone Traits Vary in Two Mouse Models of Genetic Diversity Open
Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantifi…
View article: T cells heal bone fractures with help from the gut microbiome
T cells heal bone fractures with help from the gut microbiome Open
Immune cells play an important functional role in bone fracture healing. Fracture repair is a well-choreographed process that takes approximately 21 days in healthy mice. While the process is complex, conceptually it can be divided into fo…
View article: Postnatal Osterix but not DMP1 lineage cells significantly contribute to intramembranous ossification in three preclinical models of bone injury
Postnatal Osterix but not DMP1 lineage cells significantly contribute to intramembranous ossification in three preclinical models of bone injury Open
Murine models of long-bone fracture, stress fracture, and cortical defect are used to discern the cellular and molecular mediators of intramembranous and endochondral bone healing. Previous work has shown that Osterix (Osx + ) and Dentin M…
View article: Cortical bone relationships are maintained regardless of sex and diet in a large population of LGXSM advanced intercross mice
Cortical bone relationships are maintained regardless of sex and diet in a large population of LGXSM advanced intercross mice Open
Our results indicate that variation in cortical bone phenotype in the F34 LGXSM AI mouse population can be adequately described by a reduced set of bone traits. These traits include cortical area, medullary area, bone length, ultimate forc…
View article: <scp>Loading‐induced</scp> bone formation is mediated by <i>Wnt1</i> induction in <scp>osteoblast‐lineage</scp> cells
<span>Loading‐induced</span> bone formation is mediated by <i>Wnt1</i> induction in <span>osteoblast‐lineage</span> cells Open
Mechanical loading on the skeleton stimulates bone formation. Although the exact mechanism underlying this process remains unknown, a growing body of evidence indicates that the Wnt signaling pathway is necessary for the skeletal response …
View article: Cryogel Scaffold-Mediated Delivery of Adipose-Derived Stem Cells Promotes Healing in Murine Model of Atrophic Non-Union
Cryogel Scaffold-Mediated Delivery of Adipose-Derived Stem Cells Promotes Healing in Murine Model of Atrophic Non-Union Open
Non-union is defined as the permanent failure of a bone to heal and occurs clinically in 5% of fractures. Atrophic non-unions, characterized by absent/minimal callus formation, are poorly understood and difficult to treat. We recently demo…
View article: Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling
Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling Open
Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the p…
View article: Loading-Induced Bone Formation is Mediated by <i>Wnt1</i> Induction in Osteoblast-Lineage Cells
Loading-Induced Bone Formation is Mediated by <i>Wnt1</i> Induction in Osteoblast-Lineage Cells Open
Mechanical loading on the skeleton stimulates bone formation. Although the exact mechanism underlying this process remains unknown, a growing body of evidence indicates that the Wnt signaling pathway is necessary for the skeletal response …
View article: Dmp1 Lineage Cells Contribute Significantly to Periosteal Lamellar Bone Formation Induced by Mechanical Loading But Are Depleted from the Bone Surface During Rapid Bone Formation
Dmp1 Lineage Cells Contribute Significantly to Periosteal Lamellar Bone Formation Induced by Mechanical Loading But Are Depleted from the Bone Surface During Rapid Bone Formation Open
Previous work has shown that osteoprogenitor cells (Prx1+) and pre‐osteoblasts (Osx+) contribute to mechanical loading‐induced bone formation. However, the role of mature Dmp1‐expressing osteoblasts has not been reported. In this study we …
View article: Fracture healing is delayed in the absence of gasdermin signaling
Fracture healing is delayed in the absence of gasdermin signaling Open
Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM- mediated pore formation can compromise the integrity of the …
View article: Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model
Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model Open
Nonunion is defined as the permanent failure of a fractured bone to heal, often necessitating surgical intervention. Atrophic nonunions are a subtype that are particularly difficult to treat. Animal models of atrophic nonunion are availabl…
View article: Osteoblast-Specific Wnt Secretion is Required for Skeletal Homeostasis and Loading-Induced Bone Formation in Adult Mice
Osteoblast-Specific Wnt Secretion is Required for Skeletal Homeostasis and Loading-Induced Bone Formation in Adult Mice Open
Wnt signaling is critical to many aspects of skeletal regulation, but the importance of Wnt ligands in adult bone homeostasis and the anabolic response to mechanical loading is not well documented. We inhibited Wnt ligand secretion in adul…