Mechanical Strain and Bone Cell Function: A Review

Ehrlich, P J; Lanyon, Lance E.

doi:10.1007/s001980200095

Cited by 440 publications

(325 citation statements)

References 195 publications

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“…The involvement of LPA, which signals in part through Rho, is consistent with the role of RhoA and Rho-associated kinase in driving the differentiation of osteoblasts from mesenchymal stem cells [45]. Moreover, the dependence of osteogenesis on cyclooxygenase activity is in keeping with the well-established role of prostaglandins in stimulating bone formation [46] and in mediating skeletal mechanotransduction in vivo [47].…”

Section: Expression Of P2x7 In Cells Of the Osteoblast Lineagesupporting

confidence: 69%

Expression, signaling, and function of P2X7 receptors in bone

Grol

Panupinthu

Korcok

et al. 2009

Purinergic Signalling

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Nucleotides released from cells in response to mechanical stimulation or injury may serve as paracrine regulators of bone cell function. Extracellular nucleotides bind to multiple subtypes of P2 receptors on osteoblasts (the cells responsible for bone formation) and osteoclasts (cells with the unique ability to resorb mineralized tissues). Both cell lineages express the P2X7 receptor subtype. The skeletal phenotype of mice with targeted disruption of P2rx7 points to interesting roles for this receptor in the regulation of bone formation and resorption, as well as the response of the skeleton to mechanical stimulation. This paper reviews recent work on the expression of P2X7 receptors in bone, their associated signal transduction mechanisms and roles in regulating bone formation and resorption. Areas for future research in this field are also discussed.

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Section: Expression Of P2x7 In Cells Of the Osteoblast Lineagesupporting

confidence: 69%

Expression, signaling, and function of P2X7 receptors in bone

Grol

Panupinthu

Korcok

et al. 2009

Purinergic Signalling

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“…Longer-term analysis of the effect of surgical revascularization in a larger animal model would be an advisable next step before any clinical use. Such a study must use orthotopic reconstruction of a long bone segmental resection with physiologic weightbearing, because angiogenesis, bone remodeling, and graft incorporation are dependent on mechanical loading conditions [9,16,23,25].…”

Section: Discussionmentioning

confidence: 99%

Surgical Revascularization in Structural Orthotopic Bone Allograft Increases Bone Remodeling

Willems

Kremer

Friedrich

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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Background Osseous defects reconstructed with cryopreserved structural allografts are poorly revascularized and therefore are prone to nonunion, infection, deterioration of mechanical properties, and fracture. Whether this can be mitigated by specific interventions such as intramedullary surgical revascularization has been incompletely evaluated. Questions/purposes We aimed to study surgical revascularization as a means to improve bone remodeling in cryopreserved allograft. Second, we questioned whether spatial histomorphometric differences occur in cortical bone areas after intramedullary surgical revascularization. Third, biomechanical properties of the graft-recipient construct in surgically revascularized allograft were compared with those of conventional allografts. Methods Allografts were harvested from 10 Brown Norway rats, cryopreserved, and transplanted orthotopically in a 10-mm defect in two groups of 10 Lewis rats each (major histocompatibility mismatch). In the control group, no surgical revascularization was performed, whereas in the experimental group, a saphenous arteriovenous bundle was transposed in the bone marrow cavity. Bone remodeling was measured with histomorphometry, histology, and microcomputed tomography at 16 weeks. Spatial differences were analyzed with histomorphometry. To determine biomechanical properties, load at failure and structural stiffness in bending were evaluated by the three-point bend testing. In both groups, normal values of the contralateral femur also were analyzed. Results Surgically revascularized allografts had increased bone remodeling (bone formation rate to bone surface ratio: 130 ± 47 lm 3 /lm 2 /year versus 44 ± 43 lm 3 /lm 2 / year, p = 0.006) and higher cortical osteocyte counts (18.6% ± 12.7% versus 3.1% ± 2.8%, p = 0.002) than nonrevascularized grafts. In nonrevascularized grafts, the bone formation rate to bone surface ratio was 35% of the contralateral normal values, whereas in surgically revascularized grafts, the bone formation rate to bone surface ratio in the grafts exceeded the contralateral values (110%). Microcomputed tomography did not show differences in bone volume between groups, however in both groups, bone volume was less in grafts compared with the contralateral femurs. Inner cortical bone formation rate to bone surface ratio was greater in surgically revascularized grafts (65 ± 30 lm 3 /lm 2 /year versus 13 ± 16 lm 3 /lm 2 /year in the control group, p = 0.012). Outer cortical bone formation rate to bone surface ratio also increased in surgically revascularized grafts (49 ± 31 lm 3 /lm 2 /year versus 19 ± 21 lm 3 /lm 2 /year, p = 0.032). No differences were found in load at failure and structural stiffness between both groups. In the control group, load at failure and structural stiffness were lower in grafts than in the contralateral femurs (p = 0.004 and p = 0.02, respectively). In the experimental group, surgically revascularized grafts also had lower load at failure and structural stiffness than the contralateral femurs (p = 0....

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“…The skeleton is unique in its ability to adaptively remodel in response to its perception of mechanical loading or lack of loading or disuse (reviewed in (21) (31) (18). Adaptive remodeling is defined as the constant remodeling of the bone in order to resist and withstand average daily loads.…”

Section: Osteocytes As Coordinators Of Skeletal Responses To Mechanicmentioning

confidence: 99%

Osteocytes, mechanosensing and Wnt signaling

Bonewald¹,

Johnson²

2008

Bone

927

760

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The majority of bone cell biology focuses on activity on the surface of the bone with little attention paid to the activity that occurs below the surface. However, with recent new discoveries, osteocytes, cells embedded within the mineralized matrix of bone, are becoming the target of intensive investigation. In this article, the distinctions between osteoblasts and their descendants, osteocytes, are reviewed. Osteoblasts are defined as cells that make bone matrix and osteocytes are thought to translate mechanical loading into biochemical signals that affect bone (re)modeling. Osteoblasts and osteocytes should have similarities as would be expected of cells of the same lineage, yet these cells also have distinct differences, particularly in their responses to mechanical loading and utilization of the various biochemical pathways to accomplish their respective functions. For example, the Wnt/ β-catenin signaling pathway is now recognized as an important regulator of bone mass and bone cell functions. This pathway is important in osteoblasts for differentiation, proliferation and the synthesis bone matrix, whereas osteocytes appear to use the Wnt/β-catenin pathway to transmit signals of mechanical loading to cells on the bone surface. New emerging evidence suggests that the Wnt/β-catenin pathway in osteocytes may be triggered by crosstalk with the prostaglandin pathway in response to loading which then leads to a decrease in expression of negative regulators of the pathway such as Sost and Dkk1. The study of osteocyte biology is becoming an intense area of research interest and this review will examine some of the recent findings that are reshaping our understanding of bone/bone cell biology. KeywordsOsteocytes; bone; Wnt/β-catenin signaling; Mechanosensation; Mechanical loading Osteocytes compose over 90-95% of all bone cells in the adult skeleton and are thought to respond to mechanical strain to send signals of resorption or formation (70). Osteocytes are usually regularly dispersed throughout the mineralized matrix especially in cortical bone. These cells are connected to each other and cells on the bone surface through dendritic processes that occupy tiny canals called canaliculi (For review see (17)). Not only do these cells communicate with each other and with cells on the bone surface but their dendritic processes are in contact with the bone marrow (59) giving them the potential to recruit osteoclast precursors to stimulate bone resorption (133)(12) and to regulate mesenchymal stem cell differentiation (48).

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Mechanical Strain and Bone Cell Function: A Review

Cited by 440 publications

References 195 publications

Expression, signaling, and function of P2X7 receptors in bone

Expression, signaling, and function of P2X7 receptors in bone

Surgical Revascularization in Structural Orthotopic Bone Allograft Increases Bone Remodeling

Osteocytes, mechanosensing and Wnt signaling

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