Micro-computed tomography assessment of the progression of fracture healing in mice

“…It was shown that leptin increases bone mass and reduces bone fragility in mice when administered peripherally, increasing osteoblast activity by distinct mechanisms [31][32][33]. Nevertheless, leptin can also reduce bone mass when administered into the central nervous system [31].…”

Section: Discussionmentioning

confidence: 97%

Exogenous Parathyroid Hormone-Related Peptide Promotes Fracture Healing in Lepr(−/−) Mice

Liu

Wang

et al. 2015

Calcif Tissue Int

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Diabetic osteoporosis continues to surge worldwide, increasing the risk of fracture. We have previously demonstrated that haploinsufficiency of endogenous parathyroid hormone-related peptide (PTHrP) impairs fracture healing. However, whether an exogenous supply of PTHrP can repair bone damage and accelerate fracture healing remains unclear. This study aimed to assess the efficacy and safety of PTHrP in healing fractures. Standardized mid-diaphyseal femur fractures were generated in 12-week-old wild-type and leptin receptor null Lepr(-/-) mice. After administration of PTHrP for 2 weeks, callus tissue properties were analyzed by radiography, micro-computed tomography, histology, histochemistry, immunohistochemistry, and molecular biology techniques. At 2 weeks post-fracture, cartilaginous callus areas were reduced, while total callus and bony callus areas were increased in PTHrP-treated Lepr(-/-) animals and control wild-type mice, compared with vehicle-treated Lepr(-/-) mice. The following parameters were enhanced both in Lepr(-/-) mice after treatment with PTHrP and vehicle-treated wild-type animals, compared with vehicle-treated Lepr(-/-) mice: osteoblast numbers; tissue alkaline phosphatase (ALP) and Type I collagen immunopositive areas; mRNA levels of ALP, Type I collagen, osteoprotegerin, and receptor activator for nuclear factor-κ B ligand; protein levels of Runt-related transcription factor 2 and insulin-like growth factor-1; and the number and surface of osteoclasts. In conclusion, exogenous PTHrP by subcutaneous injection promotes fracture repair in Lepr(-/-) mice by increasing callus formation and accelerating cell transformation: upregulated osteoblastic gene and protein expression, increased endochondral bone formation, osteoblastic bone formation, and osteoclastic bone resorption. However, complete repair was not obtained in PTHrP-treated Lepr(-/-) mice as in control wild-type animals.

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“…The volume of interest (VOI) was defined as a region spanning from the most proximal to the most distal extent of the tibial defect in the longitudinal direction (1mm) and therefore included the entire bone injury. Thresholding was performed on the VOI to include all of the volume inside the perimeter of the injured tibia based on a previously described protocol (O’Neill et al, 2012). The I max , I min , and J were averaged from all cross-section microCT images in the VOI using the CTan software.…”

Section: Methodsmentioning

confidence: 99%

Ecto-5′-nucleotidase (CD73) regulates bone formation and remodeling during intramembranous bone repair in aging mice

et al. 2017

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Ecto-5′-nucleotidase (CD73) generates adenosine, an osteoblast activator and key regulator of skeletal growth. It is unknown, however, if CD73 regulates osteogenic differentiation during fracture healing in adulthood, and in particular how CD73 activity regulates intramembranous bone repair in the elderly by using a CD73 knock-out (CD73−/−) mouse model. Monocortical tibial defects were created in 46 to 52-week-old wild type (WT) and CD73−/− mice. Injury repair was analyzed at post-operative days 5, 7, 14 and 21 by micro-computed tomography (micro-CT), histomorphometry, proliferating cell nuclear antigen (PCNA) immunostaining, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) histochemistry. Aged CD73 knock-out mice exhibited delayed bone regeneration and significantly reduced bone matrix deposition during bone healing detected by histomorphometry and micro-CT. Cell proliferation, ALP activity and osteoclast number were reduced in the CD73−/− mice, suggesting a combined defect in bone formation and resorption due the absence of CD73 activity in this model of intramembranous bone repair. Results from this study demonstrate that osteoblast activation through CD73 activity is essential during bone repair in aged mice, and it may present a drugable target for future biomimetic therapeutic approaches that aim at enhancing bone formation in the elderly patients.

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Micro-computed tomography assessment of the progression of fracture healing in mice

Cited by 82 publications

References 21 publications

Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification

Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification

Exogenous Parathyroid Hormone-Related Peptide Promotes Fracture Healing in Lepr(−/−) Mice

Ecto-5′-nucleotidase (CD73) regulates bone formation and remodeling during intramembranous bone repair in aging mice

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