Bone remodeling during fracture repair: The cellular picture

Schindeler, Aaron; McDonald, Michelle M.; Bokko, Paul B.; Little, David

doi:10.1016/j.semcdb.2008.07.004

Cited by 777 publications

(841 citation statements)

References 79 publications

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“…Macrophages in bone repair AC Wu et al anabolic) and remodeling, with significant overlap between each of these phases (reviewed extensively in Schindeler et al 25 ).…”

Section: Bone Repair During Fracture Healingmentioning

confidence: 99%

“…These cells then initiate a cascade of growth factors and inflammatory cytokine and chemokine production that facilitate the recruitment of inflammatory immune cells (granulocytes and inflammatory monocyte/ macrophages) that combat infection and phagocytose debris and dead cell remnants. 25 During this inflammatory event, expansion/recruitment of mesenchymal stem/progenitor/precursor cells (be they from local or more distant locations 26 ) occurs and this is followed by replacement of the hematoma with a vascularized fibrous connective tissue, known as granulation tissue. 25 Macrophages are present during the inflammatory phase of fracture healing in both humans 27 and animals.…”

Section: Macrophage Contributions To Inflammation During Fracture Repairmentioning

confidence: 99%

“…25 During this inflammatory event, expansion/recruitment of mesenchymal stem/progenitor/precursor cells (be they from local or more distant locations 26 ) occurs and this is followed by replacement of the hematoma with a vascularized fibrous connective tissue, known as granulation tissue. 25 Macrophages are present during the inflammatory phase of fracture healing in both humans 27 and animals. 12,28-31 A suite of known inflammatory macrophage cytokines that are generally associated with M1 responses can be detected at this early stage of fracture healing.…”

Section: Macrophage Contributions To Inflammation During Fracture Repairmentioning

confidence: 99%

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Unraveling macrophage contributions to bone repair

et al. 2013

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Macrophages have reemerged to prominence with widened understanding of their pleiotropic contributions to many biologies and pathologies. This includes clear advances in revealing their importance in wound healing. Here we have focused on the current state of knowledge with respect to bone repair, which has received relatively little scientific attention compared with its soft-tissue counterparts. Our detailed characterization of resident tissue macrophages residing in bone-lining tissues (osteomacs), including their pro-anabolic function, exposed a more prominent role for these cells in bone biology than previously anticipated. Recent studies have confirmed the importance of macrophages in early inflammatory processes that establish the healing cascade after bone fracture. Emerging data support that macrophage influence extends into both anabolic and catabolic phases of repair, suggesting that these cells have prolonged and diverse functions during fracture healing. More research is needed to clarify macrophage phase-specific contributions, temporospatial subpopulation variance and macrophage specific-molecular mediators. There is also clear motivation for determining whether macrophage alterations underlie compromised fracture healing. Overall, there is strong justification to pursue strategies targeting macrophages and/or their products for improving normal bone healing and overcoming failed repair.

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“…Macrophages in bone repair AC Wu et al anabolic) and remodeling, with significant overlap between each of these phases (reviewed extensively in Schindeler et al 25 ).…”

Section: Bone Repair During Fracture Healingmentioning

confidence: 99%

Section: Macrophage Contributions To Inflammation During Fracture Repairmentioning

confidence: 99%

Section: Macrophage Contributions To Inflammation During Fracture Repairmentioning

confidence: 99%

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Unraveling macrophage contributions to bone repair

et al. 2013

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“…However, inflammation is an early physiological response to a fracture that does not appear to occur during fetal bone development or during normal adolescent bone growth. 1 This suggests that events associated with inflammation may be necessary for fracture healing to occur successfully. Indeed, nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit inflammation also impair fracture healing.…”

Section: Introductionmentioning

confidence: 99%

Fracture healing and lipid mediators

O’Connor¹,

Manigrasso²,

Kim³

et al. 2014

BoneKEy Reports

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Lipid mediators regulate bone regeneration during fracture healing. Prostaglandins and leukotrienes are well-known lipid mediators that regulate inflammation and are synthesized from the O-6 fatty acid, arachidonic acid. Cyclooxygenase (COX-1 or COX-2) and 5-lipoxygenase (5-LO) catalyze the initial enzymatic steps in the synthesis of prostaglandins and leukotrienes, respectively. Inhibition or genetic ablation of COX-2 activity impairs fracture healing in animal models. Genetic ablation of COX-1 does not affect the fracture callus strength in mice, suggesting that COX-2 activity is primarily responsible for regulating fracture healing. Inhibition of cyclooxygenase activity with nonsteroidal anti-inflammatory drugs (NSAIDs) is performed clinically to reduce heterotopic ossification, although clinical evidence that NSAID treatment impairs fracture healing remains controversial. In contrast, inhibition or genetic ablation of 5-LO activity accelerates fracture healing in animal models. Even though prostaglandins and leukotrienes regulate inflammation, loss of COX-2 or 5-LO activity appears to primarily affect chondrogenesis during fracture healing. Prostaglandin or prostaglandin analog treatment, prostaglandin-specific synthase inhibition and prostaglandin or leukotriene receptor antagonism also affect callus chondrogenesis. Unlike the O-6-derived lipid mediators, lipid mediators derived from O-3 fatty acids, such as resolvin E 1 (RvE1), have anti-inflammatory activity. In vivo, RvE1 can inhibit osteoclastogenesis and limit bone resorption. Although O-6 and O-3 lipid mediators have clear-cut effects on inflammation, the role of these lipid mediators in bone regeneration is more complex, with apparent effects on callus chondrogenesis and bone remodeling.

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“…Bone fracture repair recapitulates the events of skeletogenesis and is, therefore, used as an experimental model of bone formation (Ref. 3). These processes are regulated by paracrine actions between osteoblasts and chondrocytes, and thus, proper skeletogenesis requires precise control over the differential differentiation of the MSC to these lineages.…”

mentioning

confidence: 99%

Differentiation of mesenchymal stem cells to osteoblasts and chondrocytes: a focus on adenosine receptors

Carroll

Ravid

2013

Expert Rev. Mol. Med.

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Skeletogenesis, either during development, post-injury or for maintenance, is a carefully coordinated process reliant on the appropriate differentiation of mesenchymal stem cells. Some well described, as well as a new regulator of this process (adenosine receptors), are alike in that they signal via cyclic-AMP (cAMP). This review highlights the known contribution of cAMP signalling to mesenchymal stem cell differentiation to osteoblasts and to chondrocytes. Focus has been given to how these regulators influence the commitment of the osteochondroprogenitor to these separate lineages.

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Bone remodeling during fracture repair: The cellular picture

Cited by 777 publications

References 79 publications

Unraveling macrophage contributions to bone repair

Unraveling macrophage contributions to bone repair

Fracture healing and lipid mediators

Differentiation of mesenchymal stem cells to osteoblasts and chondrocytes: a focus on adenosine receptors

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