In situ localization of collagen production by chondrocytes and osteoblasts in fracture callus.

Sandberg, M; Aro, Hannu T.; Multimäki, Petteri; Aho, Heikki; Vuorio, Eero

doi:10.2106/00004623-198971010-00012

Cited by 95 publications

(46 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The fact that we never observed cells with the morphologic characteristics of chondrocytes nor cartilage as other study already reported in this bone defect model [6,10] also supports this hypothesis. Expression of mRNA for type II collagen may in the past have been considered specific to chondrocytes [5,9], however recent investigations indicate that type II collagen mRNA is transiently expressed in osteoblasts in embryonic calvarial bone [7] and in osteoblasts of repairing fracture callus [1]. Although we have not examined the production of chondrogenic matrix in the defect area, the similarity of ossification may exist in the osteogenesis during the bone formation phase in the current model and in the intramembranous bone formation such as in calvaria [7].…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Defect Healing in Rat Diaphyseal Bone.

et al. 2001

View full text Add to dashboard Cite

ABSTRACT. Spatial expression of messenger ribonucleic acid (mRNA) for osteoblastic marker in drill hole defect healing of adult male rats was analyzed by in situ hybridization. The defect was filled with hematoma 3 days after surgery, expressing Type I collagen mRNA. Hematoma was replaced with fibrous tissue on day 7, and then with new trabecular bone on day 10, originated from the intra-medullary space, respectively. mRNA for Type I collagen, parathyroid hormone 1 receptor (PTH1R), and alkaline phosphatase (ALP) were expressed in the same cell population of fibrous tissue adjacent to newly-formed trabecular bone, and in osteoblasts lining the newlyformed trabecular bone. Hematopoietic marrow with osteoclasts subsequently invaded the region, also from the intra-medullary space, replacing all the new trabecular bone by day 21, except for a thin sub-periosteal layer. mRNA for Type I collagen, PTH1R and ALP was expressed on the periosteal surface of thin layer. Although cartilage formation was not histologically visible, mRNA for Type II collagen was weakly detected in the majority of osteoblasts lining the newly-formed trabecular bone. KEY WORDS: bone defect healing, bone formation, bone resorption, in situ hybridization, osteoblast.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Defect Healing in Rat Diaphyseal Bone.

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Ihh and type II collagen are known to be upregulated during fracture healing [41][42][43]. These genes show significant upregulation between days 7 and 14 after fracture healing.…”

Section: Identification Of Novel Gene Expression In Fracture Healingmentioning

confidence: 99%

Identification of Novel Gene Expression in Healing Fracture Callus Tissue by DNA Microarray

et al. 2008

View full text Add to dashboard Cite

Fracture healing requires controlled expression of thousands of genes. Only a small fraction of these genes have been isolated and fewer yet have been shown to play a direct role in fracture healing. The purpose of this study was threefold: (1) to develop a reproducible open femur model of fracture healing that produces consistent fracture calluses for subsequent RNA extraction, (2) to use this model to determine temporal expression patterns of known and unknown genes using DNA microarray expression profiling, and (3) to identify and validate novel gene expression in fracture healing. In the initial arm of the study, a total of 56 wild-type C57BL/6 mice were used. An open, stabilized diaphyseal femur fracture was created. Animals were killed at 1, 5, 7, 10, 14, 21, and 35 days after surgery and the femurs were harvested for analysis. At each time point, fractures were radiographed and sectioned for histologic analyses. Tissue from fracture callus at all stages following fracture yielded reproducibly large amounts of mRNA. Expression profiling revealed that genes cluster by function in a manner similar to the histologic stages of fracture healing. Based on the expression profiling of fracture tissue, temporal expression patterns of several genes known to be involved in fracture healing were verified. Novel expression of multiple genes in fracture callous tissue was also revealed including leptin and leptin receptor. In order to test whether leptin signaling is required for fracture repair, mice deficient in leptin or its receptor were fractured using the same model. Fracture calluses of mice deficient in both leptin or leptin receptor are larger than wild-type mice fractures, likely due to a delay in mineralization, revealing a previously unrecognized role of leptin signaling in fracture healing. This novel model of murine fracture repair is useful in examining both global changes in gene expression as well as individual signaling pathways, which can be used to identify specific molecular mechanisms of fracture healing.

show abstract

“…The fractures were fixed in buffered formalin, decalcified in EDTA, and embedded in paraffin (Sandberg et al, 1989). The tibias were cut longitudinally in the sagittal plane into 5 pm sections, stained with van Gieson and hematoxylin-eosin, and examined by light microscopy.…”

Section: Histoplanimetrymentioning

confidence: 99%

“…However, the fracture callus lacks the strict organization of cartilage cells into zones as seen in the epiphyseal plate. Based on our previous in situ hybridization studies (Sandberg et al, 1989), the expansion of cartilage during the growth of fracture callus occurs largely by differentiation of mesenchymal cells and less by proliferation of differentiated chondrocytes. In this respect the fracture callus thus also resembles the primary chondrification pro-cess in early development.…”

mentioning

confidence: 99%

Retarded chondrogenesis in transgenic mice with a type II collagen defect results in fracture healing abnormalities

Hiltunen

Metsäranta

Virolainen

et al. 1994

Developmental Dynamics

View full text Add to dashboard Cite

We have examined the biological and biomechanical consequences of defective type I1 collagen production for fracture repair employing a genetically engineered mouse line Dell which was generated by microinjection of a 39-kb mouse procul(I1) collagen gene construct containing a deletion of exon 7 and intron 7 (Metsaranta et al. [19921 J. Cell Biol. 118203-212). Standardized tibia1 fractures were produced in transgenic Dell mice and their nontransgenic littermates were used as controls. The fracture callus tissues were analyzed at days 7, 9, 14, 28, and 42 using radiography, histomorphometry, biomechanical testing, and Northern analysis of mRNAs for several tissuespecific matrix components. Deficient production of cartilage in Dell mice resulted in reduced radiographic callus size, smaller cross-sectional area, and impaired biomechanical properties when compared with fractures of nontransgenic control mice. The differences were most evident in 14-day fracture calluses. Consequently mRNAs for cartilage-specific type IX and X collagens and a g grecan were also reduced in Dell calluses. Levels of type I1 collagen mRNAs were unaffected since the mutated transgene produced additional type I1 collagen mRNA molecules. Further abnormalities in the fracture repair process of Dell mice were observed in callus remodeling. In the control animals a typical feature of external callus remodeling was reduction of callus size during endochondral ossification between days 14 and 28. Such reduction was not observed in the transgenic mice. Histological examination of fracture calluses s u g gested also a reduction in trabecular surface area, which was found to be even more pronounced in metaphyseal bone of Dell mice. Despite these differences the biomechanical properties of the cailuses in the two groups became similar by day 28 of fracture healing. The results thus suggest that reduced chondrogenesis due to the presence of mutated transgenes in Dell mice not only causes a temporary impairment in biomechanical properties of healing fractures but also affects later stages of callus remodeling. 0 1994 Wiley-Liss, Inc.

show abstract

In situ localization of collagen production by chondrocytes and osteoblasts in fracture callus.

Cited by 95 publications

References 0 publications

Molecular Analysis of Defect Healing in Rat Diaphyseal Bone.

Molecular Analysis of Defect Healing in Rat Diaphyseal Bone.

Identification of Novel Gene Expression in Healing Fracture Callus Tissue by DNA Microarray

Retarded chondrogenesis in transgenic mice with a type II collagen defect results in fracture healing abnormalities

Contact Info

Product

Resources

About