Characterization of a Closed Femur Fracture Model in Mice

Manigrasso, Michaele B.; O’Connor, J. P.

doi:10.1097/00005131-200411000-00006

Cited by 132 publications

(149 citation statements)

References 24 publications

Supporting

Mentioning

138

Contrasting

Order By: Relevance

“…A reproducible bone fracture model was created in the femur of the mice, according to a modification of Manigrasso's mode. 30 A lateral parapatellar knee incision on the right limb was made to expose the distal femoral chondyle. A 2-mm wedge was made using a 27-gauge needle on the interchondyle of the femur and then a 0.5-mm diameter, stainless wire was inserted in a retrograde fashion.…”

Section: Mice Animal Model Of Bone Fracturementioning

confidence: 99%

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization

Kawakami

Masaaki

Matsumoto

et al. 2013

Laboratory Investigation

View full text Add to dashboard Cite

Lnk, an intracellular adapter protein, is expressed in hematopoietic cell lineages, which has recently been proved as an essential inhibitory signaling molecule for stem cell self-renewal in the stem cell factor-c-Kit signaling pathway with enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. Moreover, the therapeutic potential of hematopoietic stem/endothelial progenitor cells (EPCs) for fracture healing has been demonstrated with mechanistic insight into vasculogenesis/angiogenesis and osteogenesis enhancement in the fracture sites. We report here, Lnk siRNAtransfected endothelial commitment of c-kit þ /Sca-1 þ /lineage À subpopulations of bone marrow cells have high EPC colony-forming capacity exhibiting endothelial markers, VE-Cad, VEGF and Ang-1. Lnk siRNA-transfected osteoblasts also show highly osteoblastic capacity. In vivo, locally transfected Lnk siRNA could successfully downregulate the expression of Lnk at the fracture site up to 1 week, and radiological and histological examination showed extremely accelerated fracture healing in Lnk siRNA-transfected mice. Moreover, Lnk siRNA-transfected mice exhibited sufficient therapeutic outcomes with intrinstic enhancement of angiogenesis and osteogenesis, specifically, the mice demonstrated better blood flow recovery in the sites of fracture. In our series of experiments, we clarified that a negatively regulated Lnk system contributed to a favorable circumstance for fracture healing by enhancing vasculogenesis/angiogenesis and osteogenesis. These findings suggest that downregulation of Lnk system may have the clinical potential for faster fracture healing, which contributes to the reduction of delayed unions or non-unions.

show abstract

Section: Mice Animal Model Of Bone Fracturementioning

confidence: 99%

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization

Kawakami

Masaaki

Matsumoto

et al. 2013

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…[16][17][18][19][20][21] The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible. [22][23][24][25][26][27][28][29][30] This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone.…”

Section: Introductionmentioning

confidence: 99%

Pseudofracture: An Acute Peripheral Tissue Trauma Model

Darwiche

Kobbe²,

Pfeifer³

et al. 2011

JoVE

View full text Add to dashboard Cite

Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; this response is often accompanied by a delayed immunosuppression that adds the clinical complications of infection and can also increase mortality. [1][2][3][4][5][6][7][8][9] Many studies have begun to assess these changes in the reactivity of the immune system following trauma. [10][11][12][13][14][15] Immunologic studies are greatly supported through the wide variety of transgenic and knockout mice available for in vivo modeling; these strains aid in detailed investigations to assess the molecular pathways involved in the immunologic responses. [16][17][18][19][20][21] The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible. [22][23][24][25][26][27][28][29][30] This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone.The pseudofracture model consists of two parts: a bilateral muscle crush injury to the hindlimbs, followed by injection of a bone solution into these injured muscles. The bone solution is prepared by harvesting the long bones from both hindlimbs of an age-and weight-matched syngeneic donor. These bones are then crushed and resuspended in phosphate buffered saline to create the bone solution.Bilateral femur fracture is a commonly used and well-established model of extremity trauma, and was the comparative model during the development of the pseudofracture model. Among the variety of available fracture models, we chose to use a closed method of fracture with soft tissue injury as our comparison to the pseudofracture, as we wanted a sterile yet proportionally severe peripheral tissue trauma model. 31 Hemorrhagic shock is a common finding in the setting of severe trauma, and the global hypoperfusion adds a very relevant element to a trauma model. [32][33][34][35][36] The pseudofracture model can be easily combined with a hemorrhagic shock model for a multiple trauma model of high severity. 37 Protocol

show abstract

“…In the first, the femur is osteotomized using an open surgical approach (open models); [7][8][9][10] in the second, the femur is fractured using a three-point bending device (closed models). 3,[11][12][13][14][15][16] In the closed models, mostly conventional pins, for example, pinched off injection needles, are applied for fracture stabilization, which do not provide a sufficient rotational stability. 15,[17][18][19][20] In some studies the fracture has even been left unstabilized.…”

mentioning

confidence: 99%

“…3,[11][12][13][14][15][16] In the closed models, mostly conventional pins, for example, pinched off injection needles, are applied for fracture stabilization, which do not provide a sufficient rotational stability. 15,[17][18][19][20] In some studies the fracture has even been left unstabilized. 21 It is well known, especially in humans and large animal models, that mechanical conditions, particularly the rotational stiffness of the stabilized fracture, influence the course of fracture healing.…”

mentioning

confidence: 99%

Ex vivo analysis of rotational stiffness of different osteosynthesis techniques in mouse femur fracture

Histing

Holstein

Garcia

et al. 2009

Journal Orthopaedic Research

View full text Add to dashboard Cite

The various molecular mechanisms of cell regeneration and tissue healing can best be studied in mouse models with the availability of a wide range of monoclonal antibodies and gene‐targeted animals. The influence of the mechanical stability of individual stabilization techniques on the molecular mechanisms of fracture healing has not been completely elucidated yet. Although during recent years several osteosynthesis techniques have been introduced in mouse fracture models, no comparative study on fracture stabilization is available yet. We therefore analyzed herein in a standardized ex vivo setup the rotational stiffness of seven different osteosynthesis techniques using osteotomized right cadaver femora of CD‐1 mice. Uninjured femora without osteotomy served as controls. Femur stabilization with a locking plate or an external fixator resulted in a rotational stiffness almost similar to the intact femur. The use of a “pin‐clip” device, a “locking nail,” a “mouse nail,” or an “intramedullary screw” produced a lower torsional stiffness, which, however, was still significantly higher than that achieved with the widely applied conventional pin. By the use of the presented data a more specific choice of stabilization technique will be possible according to the various questions concerning molecular aspects in fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1152–1156, 2009

show abstract

Characterization of a Closed Femur Fracture Model in Mice

Cited by 132 publications

References 24 publications

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization

Pseudofracture: An Acute Peripheral Tissue Trauma Model

Ex vivo analysis of rotational stiffness of different osteosynthesis techniques in mouse femur fracture

Contact Info

Product

Resources

About