Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2

Champagne, Catherine M.; Takebe, Jun; Offenbacher, Steven; Cooper, Lyndon F.

doi:10.1016/s8756-3282(01)00638-x

Cited by 321 publications

(267 citation statements)

References 17 publications

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“…The increased bioburden imparted by bacterial colonization also may contribute to the proinflammatory microenvironment, and we noted a significantly increased rate of critical bacterial colonization in the HO cohort, similar to that previously described in combat casualties [15]. The expression of mitogenic growth factors and proinflammatory cytokines has also been shown to be upregulated during bacterial colonization and specifically after exposure to lipopolysaccharide [6].…”

Section: Gene Upregulation In Patients Who Developed Heterotopic Ossisupporting

confidence: 87%

“…Differences in gene expression between groups evaluated using the Mann-Whitney U test; ALPL = alkaline phosphatase, COL = collagen alpha, COMP = collagen oligometric matrix protein, CSF = colony stimulating factor, MMP = matrix metalloproteinase; SMAD1 = SMAD family member. upregulated at sites of muscular damage and soft tissue injury [6,25,41]. Overactive BMP signaling has been implicated in the development of HO [25,46,48].…”

Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

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Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Evans

Potter

Brown

et al. 2013

Clin Orthop Relat Res

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Background Heterotopic ossification (HO) is a frequent complication of modern wartime extremity injuries. The biological mechanisms responsible for the development of HO in traumatic wounds remain elusive. Question/purposes The aims of our study were to (1) characterize the expression profile of osteogenesis-related gene transcripts in traumatic war wounds in which HO developed; and (2) determine whether expression at the mRNA level correlated with functional protein expression and HO formation. Methods Biopsy specimens from 54 high-energy penetrating extremity wounds obtained at the initial and final surgical débridements were evaluated. The levels of selected osteogenic-related gene transcripts from RNA extracts were assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. As a result of its key role in osteogenesis, the concentration of BMP-2 in the effluent of 29 wounds also was determined. Conclusions Important differences exist in the osteogenic gene expression profile of wounds in which HO developed compared with wounds in which it did not develop. The upregulation of multiple osteogenesis-related gene transcripts indicates the presence of a proosteogenic environment necessary for ectopic bone formation in traumatic wounds.

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Section: Gene Upregulation In Patients Who Developed Heterotopic Ossisupporting

confidence: 87%

Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Evans

Potter

Brown

et al. 2013

Clin Orthop Relat Res

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“…21 On this basis, it has been suggested that osseous healing is inhibited by conditions that promote proinflammatory activity of the macrophage. 20 This suggestion is underlined by our study when it comes to SaPG.…”

Section: Discussionsupporting

confidence: 53%

“…1 Therefore, it has been hypothesized that the macrophage cell lines have a central role in wound and fracture healing. 20 However, the induction of inflammatory cytokines and fibrosis promoting growth factors by stimulated macrophages suggests a prominent osteolytic effect as the macrophages loses its ability to synthesize BMP-2 under proinflammatory conditions. 21 On this basis, it has been suggested that osseous healing is inhibited by conditions that promote proinflammatory activity of the macrophage.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus peptidoglycan impairs fracture healing: An experimental study in rats

Reikerås

Wang

Foster

et al. 2006

Journal Orthopaedic Research

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Stahylococcus aureus is the common organism causing musculoskeletal infectons. Stahylococcus aureus peptidoglycan (SaPG) has been identified to increase the acute inflammatory response to wounding, increase reparative granulation tissue, and improve healing. The healing of bone fractures is a balanced process of granulation tissue that is calcified to obtain increasing stability. By increasing reparative collagen accumulation, however, SaPG may induce a shift towards immature fibrous callus production. Therefore, it was our hypothesis that SaPG would impair bone healing after fracture. In three groups, each of nine rats, a middiaphyseal osteotomy/ fracture of the femoral bone was performed and then nailed. In one group of animals, SaPG was applied locally at the fracture site, and in another group SaPG was applied intraperitoneally (systemically). Control littermate received saline. The animals were sacrificed after 6 weeks, and the mechanical characteristics of the healing osteotomies were evaluated. We found that application of SaPG locally induced a hypertrophic and immature callus as evaluated by callus production, by bone mineral content and density, and by bending moment and rigidity. In the rats given SaPG intraperitoneally, bone healing went uneventful compared to the control rats. Collectively, these data show that SaPG induces an alteration in the normal bone healing response towards a less calcified callus production. ß

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“…Likewise, excessive stimulation of macrophages with lipopolysaccharide can decrease their production of BMP-2 causing a delayed bone healing [108]. Additionally, within a chronic inflammatory milieu, monocytes have a higher potential to differentiate into osteoclasts through TNF-a dependent mechanism [109].…”

Section: The Uncontrolled Immune Cell Response and Defective Bone Heamentioning

confidence: 99%

The roles of immune cells in bone healing; what we know, do not know and future perspectives

El-Jawhari

Jones

Giannoudis

2016

Injury

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Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2

Cited by 321 publications

References 17 publications

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Staphylococcus aureus peptidoglycan impairs fracture healing: An experimental study in rats

The roles of immune cells in bone healing; what we know, do not know and future perspectives

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