Major fibrillar collagens and fibronectin in an experimental nonunion: An immunohistochemical study

Hietaniemi, Kalevi; Lehto, Matti; Paavolainen, Pekka

doi:10.3109/17453679808997795

Cited by 11 publications

(5 citation statements)

References 11 publications

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“…In the pseudarthrosis model used in the present study, cartilage synthesis reached its maximum at 7 weeks. The stimulus of endochondral ossification becomes, however, exhausted, and the fracture gap develops into an inactive fibrous scar (Ekholm et al 1995;Hietaniemi et al 1998). As in stable mouse fracture repair, NF1 mRNA and protein were expressed in resting and hypertrophic cartilages in experimental pseudarthrosis, in particular at week 7, correlating with maximal cartilage-specific gene expression.…”

Section: Discussionmentioning

confidence: 99%

NF1 Gene Expression in Mouse Fracture Healing and in Experimental Rat Pseudarthrosis

Kuorilehto

Ekholm

Nissinen

et al. 2006

J Histochem Cytochem.

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(PP) S U M M A R Y Neurofibromatosis type 1 (NF1) is an inherited disease with an incidence of about 1:3000 worldwide. Approximately half of all patients with NF1 present osseous manifestations, which can vary from mild to severely debilitating changes such as congenital pseudarthrosis. In the present study, fracture healing of mouse tibia was followed and specimens were collected 5, 9, 14, and 22 days postoperatively. Experimental pseudarthrosis of rat was followed up to 15 weeks postoperatively. In situ hybridization and immunohistochemistry were used to demonstrate expression of NF1 tumor suppressor and phosphorylated p44/42 mitogen-activated protein kinase (MAPK), an indicator of the Ras-MAPK pathway. The results showed that ossified callus was formed in mouse fracture 22 days after the operation. The final outcome of rat pseudarthrosis was detected 9 weeks after the operation, presenting abundant cartilaginous callus at the pseudarthrosis. NF1 gene expression was noted in the maturing and in the hypertrophic cartilages during normal mouse fracture healing, and in rat pseudarthrosis. Phosphorylated p44/42 MAPK was detected in a subpopulation of the hypertrophic chondrocytes in both models. Furthermore, positive labeling for NF1 mRNA and protein was detected in endothelium in both the pseudarthrosis and in the fracture. In conclusion, NF1 gene expression and function are needed for normal fracture healing, possibly restraining excessive Ras-MAPK pathway activation.

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Section: Discussionmentioning

confidence: 99%

NF1 Gene Expression in Mouse Fracture Healing and in Experimental Rat Pseudarthrosis

Kuorilehto

Ekholm

Nissinen

et al. 2006

J Histochem Cytochem.

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“…80 In the early phase, at 1 week, collagen type I was localized subperiosteally in close proximity to lamellar structured new bone. Thereafter, collagen type I was identified at newly formed lamellar periosteal bone, as well as at the endochondral ossification front.…”

Section: Causes and Characteristics Of Failed Fracture Healing Rementioning

confidence: 93%

“…If the repair process was impaired by instability, other findings indicate a time-limited healing potency of a fracture. 80 The normal healing process stops and matrix mineralization of the callus is delayed, leading to production of fibroblasts, collagen type III, and fibronectin. Thus, production of collagens and other matrix components is initiated and leads to healing with scar tissue and nonunion.…”

Section: Causes and Characteristics Of Failed Fracture Healing Rementioning

confidence: 99%

Recent Advances in the Use of Serological Bone Formation Markers to Monitor Callus Development and Fracture Healing

Coulibaly

Sietsema

Burgers

et al. 2010

Crit Rev Eukar Gene Expr

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The failure of an osseous fracture to heal, or the development of a nonunion, is common; however, current diagnostic measures lack the capability of early and reliable detection of such events. Analyses of radiographic imaging and clinical examination, in combination, remain the gold standard for diagnosis; however, these methods are not reliable for early detection. Delayed diagnosis of a nonunion is costly from both the patient and treatment standpoints. In response, repeated efforts have been made to identify bone metabolic markers as diagnostic or prognostic tools for monitoring bone healing. Thus far, the evidence regarding a correlation between the kinetics of most bone metabolic markers and nonunion is very limited. With the aim of classifying the role of biological pathways of bone metabolism and of understanding bone conditions in the development of osteoporosis, advances have been made in our knowledge of the molecular basis of bone remodeling, fracture healing, and its failure. Procollagen type I amino-terminal propeptide has been shown to be a reliable bone formation marker in osteoporosis therapy and its kinetics during fracture healing has been recently described. In this article, we suggest that procollagen type I amino-terminal propeptide presents a good opportunity for early detection of nonunion. We also review the role and potential of serum PINP, as well as other markers, as indications of fracture healing.

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“…As long bone nonunions are clinically diagnosed after 6–9 months of nonhealing (i.e., three‐times the normal healing time) and in healthy mice, normal healing of a femur fracture occurs within 4 weeks, it has been proposed that confirmation of nonunion should be based on evaluation at 12 weeks post‐fracture 14,40 . Despite some early studies focused on creating hypertrophic nonunions in rats and dogs, 41–44 the majority of animal models have targeted atrophic nonunions due to difficulty treating these clinically. Animal models of atrophic nonunion have focused on modeling fractures that will not heal over the animals lifetime, typically induced both mechanically and physically 25 .…”

Section: In Vivo Models Of Bone Defectsmentioning

confidence: 99%

Animal models of impaired long bone healing and tissue engineering‐ and cell‐based in vivo interventions

Hixon

Miller

2022

Journal Orthopaedic Research

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Bone healing after injury typically follows a systematic process and occurs spontaneously under appropriate physiological conditions. However, impaired long bone healing is still quite common and may require surgical intervention. Various complications can result in different forms of impaired bone healing including nonunion, critical‐size defects, or stress fractures. While a nonunion may occur due to impaired biological signaling and/or mechanical instability, a critical‐size defect exhibits extensive bone loss that will not spontaneously heal. Comparatively, a stress fracture occurs from repetitive forces and results in a non‐healing crack or break in the bone. Clinical standards of treatment vary between these bone defects due to their pathological differences. The use of appropriate animal models for modeling healing defects is critical to improve current treatment methods and develop novel rescue therapies. This review provides an overview of these clinical bone healing impairments and current animal models available to study the defects in vivo. The techniques used to create these models are compared, along with the outcomes, to clarify limitations and future objectives. Finally, rescue techniques focused on tissue engineering and cell‐based therapies currently applied in animal models are specifically discussed to analyze their ability to initiate healing at the defect site, providing information regarding potential future therapies. In summary, this review focuses on the current animal models of nonunion, critical‐size defects, and stress fractures, as well as interventions that have been tested in vivo to provide an overview of the clinical potential and future directions for improving bone healing.

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Major fibrillar collagens and fibronectin in an experimental nonunion: An immunohistochemical study

Cited by 11 publications

References 11 publications

NF1 Gene Expression in Mouse Fracture Healing and in Experimental Rat Pseudarthrosis

NF1 Gene Expression in Mouse Fracture Healing and in Experimental Rat Pseudarthrosis

Recent Advances in the Use of Serological Bone Formation Markers to Monitor Callus Development and Fracture Healing

Animal models of impaired long bone healing and tissue engineering‐ and cell‐based in vivo interventions

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