Effects of Pleiotrophin (PTN) Over-expression on Mouse Long Bone Development, Fracture Healing and Bone repair

2005 ◽  
Vol 76 (4) ◽  
pp. 299-306 ◽  
Author(s):  
G. Li ◽  
J. R. Bunn ◽  
M. T. Mushipe ◽  
Q. He ◽  
X. Chen
Author(s):  
Gregory Lowen ◽  
Katherine Garrett ◽  
Moore-Lotridge Stephanie ◽  
Sasidhar Uppuganti ◽  
Scott A. Guelcher ◽  
...  

Abstract Delayed long bone fracture healing and nonunion continue to be a significant socioeconomic burden. While mechanical stimulation is known to be an important determinant of the bone repair process, understanding how the magnitude, mode, and commencement of interfragmentary strain (IFS) affect fracture healing can guide new therapeutic strategies to prevent delayed healing or non-union. Mouse models provide a means to investigate the molecular and cellular aspects of fracture repair, yet there is only one commercially available, clinically-relevant, locking intramedullary nail (IMN) currently available for studying long bone fractures in rodents. Having access to alternative IMNs would allow a variety of mechanical environments at the fracture site to be evaluated, and the purpose of this proof-of-concept finite element analysis study is to identify which IMN design parameters have the largest impact on IFS in a murine transverse femoral osteotomy model. Using the dimensions of the clinically relevant IMN as a guide, the nail material, distance between interlocking screws, and clearance between the nail and endosteal surface were varied between simulations. Of these parameters, changing the nail material from stainless steel (SS) to polyetheretherketone (PEEK) had the largest impact on IFS. Reducing the distance between the proximal and distal interlocking screws substantially affected IFS only when nail modulus was low. Therefore, IMNs with low modulus (e.g., PEEK) can be used alongside commercially available SS nails to investigate the effect of initial IFS or stability on fracture healing with respect to different biological conditions of repair in rodents.


2017 ◽  
Vol 139 (11) ◽  
Author(s):  
Brett S. Klosterhoff ◽  
Keat Ghee Ong ◽  
Laxminarayanan Krishnan ◽  
Kevin M. Hetzendorfer ◽  
Young-Hui Chang ◽  
...  

Bone development, maintenance, and regeneration are remarkably sensitive to mechanical cues. Consequently, mechanical stimulation has long been sought as a putative target to promote endogenous healing after fracture. Given the transient nature of bone repair, tissue-level mechanical cues evolve rapidly over time after injury and are challenging to measure noninvasively. The objective of this work was to develop and characterize an implantable strain sensor for noninvasive monitoring of axial strain across a rodent femoral defect during functional activity. Herein, we present the design, characterization, and in vivo demonstration of the device’s capabilities for quantitatively interrogating physiological dynamic strains during bone regeneration. Ex vivo experimental characterization of the device showed that it possessed promising sensitivity, signal resolution, and electromechanical stability for in vivo applications. The digital telemetry minimized power consumption, enabling extended intermittent data collection. Devices were implanted in a rat 6 mm femoral segmental defect model, and after three days, data were acquired wirelessly during ambulation and synchronized to corresponding radiographic videos, validating the ability of the sensor to noninvasively measure strain in real-time. Together, these data indicate the sensor is a promising technology to quantify tissue mechanics in a specimen specific manner, facilitating more detailed investigations into the role of the mechanical environment in dynamic bone healing and remodeling processes.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yang Li ◽  
Shuting Yang ◽  
Ling Qin ◽  
Shuying Yang

AbstractChondrogenesis is a major contributor to skeletal development and maintenance, as well as bone repair. Transcriptional coactivator with PDZ-binding motif (TAZ) is a key regulator of osteogenesis and adipogenesis, but how TAZ regulates chondrogenesis and skeletal development remains undefined. Here, we found that TAZ expression is gradually increased during chondrogenic differentiation. Deletion of TAZ in chondrocyte lineage impaired articular and growth plate, as well as the bone development in TAZ-deficient mice. Consistently, loss of TAZ impaired fracture healing. Mechanistically, we found that ectopic expression of TAZ markedly promoted chondroprogenitor proliferation, while deletion of TAZ impaired chondrocyte proliferation and differentiation. TAZ associated with Sox5 to regulate the expression and stability of Sox5 and downstream chondrocyte marker genes’ expression. In addition, overexpression of TAZ enhanced Col10a1 expression and promoted chondrocyte maturation, which was blocked by deletion of TAZ. Overall, our findings demonstrated that TAZ is required for skeletal development and joint maintenance that provided new insights into therapeutic strategies for fracture healing, heterotopic ossification, osteoarthritis, and other bone diseases.


2021 ◽  
Vol 11 (12) ◽  
pp. 2337-2345
Author(s):  
Junhui Lai ◽  
Qin Yang ◽  
Ruining Liang ◽  
Weijun Guan ◽  
Xiuxia Li

The growth plate is essential in long bone formation and contains a wealth of skeletal stem cells (SSCs). Though the origin and the mechanism for SSCs generation remain uncertain, recent studies demonstrate the transition from cartilage to bone that in the lineage for bone development. SSCs possesses the ability to differentiate into bone and cartilage in vitro. In this research, we aimed to isolate and culture the skeletal stem cells from bovine cattle and then studied its biological characterization. The results showed that these bovine SSCs are positive for PDPN+CD73+CD164+CD90+CD44+ cell surface bio-markers, they are capable of self-renewal and differentiation. Our dates proved that SSCs exists in bovine’s long bone.


2021 ◽  
Vol 11 (2) ◽  
pp. 229-239
Author(s):  
Yun Li ◽  
Guanghua Liu ◽  
Feng Xiao ◽  
Wenqin Gu ◽  
Zhengdong Gao ◽  
...  

We did this research to observe the effect of LIPUS on long bone fracture repair and caveolin-1, β-catenin signaling expression in the radius defects of rabbits, to explore its possible molecular mechanisms. 24 male New Zealand rabbits with bilateral radial bone defects were divided into 4 groups randomly, n = 6. The right side had daily LIPUS exposure for 20 minutes, while the left received sham treatment. After 7, 14, 21, 28 days, respectively, fracture healing was observed by X-ray imaging and Dual Energy X-ray Absorptiometry (DXA) scan, specimens were harvested for histology, immunohistochemistry, and gene expression analysis. We found that LIPUS brought forward endochondral ossification, increased the bone callus size without changes in Bone Mineral Density (BMD). The caveolin-1 expression increased first then decreased, while the β-catenin kept growing during the process. These demonstrated that caveolin-1 participated in fracture healing accelerated by LIPUS, which was speculated to play a dual role in β-catenin signaling expression.


Author(s):  
Viktoriia KAMSKA ◽  
Edward B. DAESCHLER ◽  
Jason P. DOWNS ◽  
Per E. AHLBERG ◽  
Paul TAFFOREAU ◽  
...  

ABSTRACTHyneria lindae is one of the largest Devonian sarcopterygians. It was found in the Catskill Formation (late Famennian) of Pennsylvania, USA. The current study focuses on the palaeohistology of the humerus of this tristichopterid and supports a low ossification rate and a late ossification onset in the appendicular skeleton. In addition to anatomical features, the large size of the cell lacunae in the cortical bone of the humerus mid-shaft may suggest a large genome size and associated neotenic condition for this species, which could, in turn, be a partial explanation for the large size of H. lindae. The low metabolism of H. lindae revealed here by bone histology supports the hypothesis of an ambush predatory behaviour. Finally, the lines-of-arrested-growth pattern and late ossification of specimen ANSP 21483 suggest that H. lindae probably had a long juvenile stage before reaching sexual maturity. Although very few studies address the life-history traits of stem tetrapods, they all propose a slow limb development for the studied taxa despite different ecological conditions and presumably distinct behaviours. The bone histology of H. lindae would favour the hypothesis that a slow long-bone development could be a general character for stem tetrapods.


Author(s):  
Christina Ekegren ◽  
Elton Edwards ◽  
Richard de Steiger ◽  
Belinda Gabbe

Fracture healing complications are common and result in significant healthcare burden. The aim of this study was to determine the rate, costs and predictors of two-year readmission for surgical management of healing complications (delayed, mal, non-union) following fracture of the humerus, tibia or femur. Humeral, tibial and femoral (excluding proximal) fractures registered by the Victorian Orthopaedic Trauma Outcomes Registry over five years (n = 3962) were linked with population-level hospital admissions data to identify two-year readmissions for delayed, mal or non-union. Study outcomes included hospital length-of-stay (LOS) and inpatient costs. Multivariable logistic regression was used to determine demographic and injury-related factors associated with admission for fracture healing complications. Of the 3886 patients linked, 8.1% were readmitted for healing complications within two years post-fracture, with non-union the most common complication and higher rates for femoral and tibial shaft fractures. Admissions for fracture healing complications incurred total costs of $4.9 million AUD, with a median LOS of two days. After adjusting for confounders, patients had higher odds of developing complications if they were older, receiving compensation or had tibial or femoral shaft fractures. Patients who are older, with tibial and femoral shaft fractures should be targeted for future research aimed at preventing complications.


Author(s):  
Brandon G. Santoni ◽  
Rohat Melik ◽  
Emre Unal ◽  
Nihan Kosku Perkgoz ◽  
Debra A. Kamstock ◽  
...  

Orthopaedic extremity injuries present a large medical and financial burden to the United States and world-wide communities [1]. Approximately six million long bone fractures are reported annually in the United States and approximately 10% of these fractures do not heal properly. Though the exact mechanism of impaired healing is poorly understood, many of these non-unions result when there is a communited condition that does not proceed through a stabilized healing pathway [2]. Currently, clinicians may monitor healing visually by radiographs, or via manual manipulation of the bone at the fracture [3]. Unfortunately, the course of aberrant fracture healing is not easily diagnosed in the early period when standard radiographic information of the fracture is not capable of discriminating the healing pathway. Manual assessment of fracture healing is also an inadequate diagnostic tool in the early stages of healing [4].


2021 ◽  
Vol 10 (16) ◽  
pp. 3554
Author(s):  
Dionysios J. Papachristou ◽  
Stavros Georgopoulos ◽  
Peter V. Giannoudis ◽  
Elias Panagiotopoulos

Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects.


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