Wnt3a Reestablishes Osteogenic Capacity to Bone Grafts from Aged Animals

Leucht, Philipp; Jiang, Jie; Cheng, Du; Liu, Bo; Dhamdhere, Girija; Fang, Mark Y.; Monica, Stefanie D.; Urena, Jonathan J.; Cole, Whitney; Smith, Lane R.; Castillo, Alesha B.; Longaker, Michael T.; Helms, Jill A.

doi:10.2106/jbjs.l.01502

Cited by 52 publications

(77 citation statements)

References 75 publications

(88 reference statements)

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“…A circumferential, full-thickness defect with a 2-mm diameter calvarial defect was created as described in mice [38].…”

Section: Skeletal Surgeriesmentioning

confidence: 99%

“…In previous work we cataloged the distribution of canonical and non-canonical Wnt ligands in the intact and injured skeleton, and this analysis revealed that Wnt3a was most broadly expressed [37]. Further, the expression level of Wnt3a was the most severely affected by aging [38]. Consequently, our study here focused on delivery of WNT3A to autografts from aged animals.…”

Section: Introductionmentioning

confidence: 99%

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Reengineering autologous bone grafts with the stem cell activator WNT3A

et al. 2015

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“…A circumferential, full-thickness defect with a 2-mm diameter calvarial defect was created as described in mice [38].…”

Section: Skeletal Surgeriesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reengineering autologous bone grafts with the stem cell activator WNT3A

et al. 2015

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“…This is in line with a recent published work of Oliver et al [37], where the fracture callus in the OVX group was filled with soft tissue and cartilage remnants. Fatty degradation of bone marrow in the elderly, which is associated with a decreased load-bearing capacity and accordingly a higher osteoporotic-related fracture risk, is regulated by beta-catenin-dependent Wnt signaling [8]. This pathway determines mesenchymal stem cells to differentiate into an osteogenic or adipogenic lineage, thus a manipulation of this signaling can influence the bone mass [8].…”

Section: Osteoporotic Bone Healingmentioning

confidence: 99%

“…Fatty degradation of bone marrow in the elderly, which is associated with a decreased load-bearing capacity and accordingly a higher osteoporotic-related fracture risk, is regulated by beta-catenin-dependent Wnt signaling [8]. This pathway determines mesenchymal stem cells to differentiate into an osteogenic or adipogenic lineage, thus a manipulation of this signaling can influence the bone mass [8]. In osteoporotic bone, bone morphogenetic proteins (BMP) play also an important role by regulation of the BMPWnt-RANKL axis.…”

Section: Osteoporotic Bone Healingmentioning

confidence: 99%

“…Many efforts have been undertaken to support fracture healing and replace destroyed bone with biomaterials. Until now autogenous cancellous bone grafting is the gold standard to stimulate bone healing in fracture defects, despite of the resulting comorbidities at the donor site and the impaired osteogenic potential in elderly bone grafts [8] and especially in an osteoporotic bone status [9].…”

Section: Introductionmentioning

confidence: 99%

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Biomaterials for enhancement of bone healing in osteoporotic fractures

Thormann¹,

Ray

Sommer

et al. 2013

BioNanoMaterials

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Osteoporosis and osteoporotic fractures have a high impact on the quality of life of patients and on the financial aspects of Western health care systems. There is a tremendous need for improvement of the treatment outcome in osteoporotic fracture patients and biomaterials are of interest to stimulate fracture healing in those patients. For adequate characterization of biomaterials for the indication of osteoporotic fractures a clinically relevant animal model with a fracture defect in the metaphyseal region of a long bone in an osteoporotic animal is required. We recently developed a 3-5 mm wedge shaped osteotomy model in the distal metaphysis of the femur in osteoporotic rats. There are different biomaterials approaches to stimulate fracture healing in osteoporotic fractures and recently published results suggest that the composite implants from osteoconductive carriers combined with osteoanabolic agents, e.g., strontium-modified calcium phosphate cement, can enhance new bone formation. Further in vivo and clinical research will be necessary in the future for introduction of new and different types of biomaterials for osteoporotic fracture patients into all day clinical practice.

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Granulation Tissue Eroding the Subchondral Bone Also Promotes New Bone Formation in Ankylosing Spondylitis

Bleil

Maier

Hempfing

et al. 2016

Arthritis & Rheumatology

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Objective. We previously suggested that fibroblastrich granulation tissue eroding the subchondral bone is instrumental in the joint remodeling that occurs in ankylosing spondylitis (AS). The purpose of this study was to determine if this granulation tissue also carries boneforming capabilities, which we approached by searching for bone-forming cells (hypertrophic chondrocytes, osteoblasts) in its vicinity. We also assessed adipogenic tissue transformation, which has been suggested to be an intermediate feature in AS bone formation based on imaging studies.Methods. The facet joints of AS patients, osteoarthritis (OA) patients, and autopsy subjects (controls) were screened for subchondral granulation tissue. We searched for hypertrophic chondrocytes by assessing RUNX-2, type X collagen, and matrix metalloproteinase 13 (MMP-13) expression, for osteoblasts by analyzing RUNX-2, CD56, and type I collagen expression, as well as for signs of new bone formation. Adipocytes and lipid accumulation were assessed in Safranin O-stained sections.Results. In the joints of AS and OA patients, RUNX-2-positive cells were found to be lining the granulation tissue. These cells coexpressed type I collagen but lacked type X collagen and MMP-13 expression, confirming their osteoblastic nature. In 91% of AS joints and in 20% of OA joints (P < 0.05), we observed foci of new bone formation at contact zones between the granulation tissue and the cartilage. Joints containing bony spots showed greater replacement of the adjacent bone marrow by granulation tissue than did joints without bone formation (P < 0.05). The granulation tissue often contained adipocytes and lipid accumulations.

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Wnt3a Reestablishes Osteogenic Capacity to Bone Grafts from Aged Animals

Cited by 52 publications

References 75 publications

Reengineering autologous bone grafts with the stem cell activator WNT3A

Reengineering autologous bone grafts with the stem cell activator WNT3A

Biomaterials for enhancement of bone healing in osteoporotic fractures

Granulation Tissue Eroding the Subchondral Bone Also Promotes New Bone Formation in Ankylosing Spondylitis

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