scholarly journals Deciphering an extreme morphology: bone microarchitecture of the hero shrew backbone (Soricidae: Scutisorex )

2020 ◽  
Vol 287 (1926) ◽  
pp. 20200457 ◽  
Author(s):  
Stephanie M. Smith ◽  
Kenneth D. Angielczyk

Biological structures with extreme morphologies are puzzling because they often lack obvious functions and stymie comparisons to homologous or analogous features with more typical shapes. An example of such an extreme morphotype is the uniquely modified vertebral column of the hero shrew Scutisorex , which features numerous accessory intervertebral articulations and massively expanded transverse processes. The function of these vertebral structures is unknown, and it is difficult to meaningfully compare them to vertebrae from animals with known behavioural patterns and spinal adaptations. Here, we use trabecular bone architecture of vertebral centra and quantitative external vertebral morphology to elucidate the forces that may act on the spine of Scutisorex and that of another large shrew with unmodified vertebrae ( Crocidura goliath ). X-ray micro-computed tomography (µCT) scans of thoracolumbar columns show that Scutisorex thori is structurally intermediate between C. goliath and S. somereni internally and externally, and both Scutisorex species exhibit trabecular bone characteristics indicative of higher in vivo axial compressive loads than C. goliath. Under compressive load, Scutisorex vertebral morphology is adapted to largely restrict bending to the sagittal plane (flexion). Although these findings do not solve the mystery of how Scutisorex uses its byzantine spine in vivo , our work suggests potentially fruitful new avenues of investigation for learning more about the function of this perplexing structure.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Gilberto Li Feng ◽  
Marc Grynpas ◽  
Jane Mitchell

Abstract Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by elevated parathyroid hormone (PTH) levels and hypercalcemia caused by the overactive parathyroid glands, resulting in negative impacts on the skeleton including bone loss and increased bone fragility1. PTH binds and activates parathyroid hormone type 1 receptor (PTH1R) which primary couples to Gαs, stimulating the downstream effectors that mediate bone remodeling processes2. PTH1R activity is regulated by arrestins, specially β-arrestin2 (β-arr2), through signal termination and receptor internalization2. Previously, we have seen anabolic effects of hyperparathyroidism (cPTH) on trabecular bone in mice overexpressing Gαs3. We hypothesized that increased Gαs protein levels in osteoblasts outcompete β-arr binding to PTH1R, leading to reduced signal termination and increased bone formation. To test this hypothesis, we are testing if the deletion of β-arr2 will also result in an anabolic response to cPTH in this study. The response of β-arr2 knockout (KO) mice to cPTH have yet to be documented. The hypothesis of this study is that β-arr2 KO mice treated with cPTH will exhibit anabolic effects on the trabecular bone. Nine-week-old wild-type (WT) C57BL/6 and β-arr2 KO mice were treated for 14 days with either rPTH1-34 (80ng/g/day) or saline (PBS) using micro-osmotic pumps to simulate hyperparathyroidism. There are 8 groups (n=10 per group) including both sexes, 2 genotypes (WT and KO), and 2 treatment groups (PTH and PBS). Two 30 mg/kg doses of 0.6% calcein green were administered subcutaneously to mice at 7 and 2 days prior to euthanasia to label bones. Decalcified tibiae were embedded in paraffin for histological analysis. Undecalcified tibiae were embedded in plastic for dynamic histomorphometry. Micro-computed tomography (μCT) was used to access bone microarchitecture of femurs and vertebrae followed by biomechanical testing of bone strength. The μCT data of distal femurs show that cPTH treatment increased bone volume in female KO mice (6.864 ± 2.318 vs 4.690 ± 1.555 %; P= 0.0328; n=9 per group) and maintained bone in male KO mice (13.37 ± 2.860 vs 13.38 ± 3.135; P= 0.9968, n= 10) compared to control. Histological analysis show higher osteoclastic activity in both sexes and genotypes when treated with cPTH, suggesting that the anabolic response may be at the level of osteoblasts and osteocytes. These promising results support our hypothesis that arrestin-mediated PTH receptor downregulation plays an importance role in bone weakness associated with hyperparathyroidism. These studies are important for understanding the clinical phenotype of PHPT patients and suggest that inhibition of β-arr2 in PHPT could be a path for drug therapy. References: (1) Mosekilde L. Clin Endocrinol 2008;69:1-9. (2) Ferrari SL et al., J Biol Chem 1999; 274:29968–29975 (3) Zhang L. PhD thesis University of Toronto, 2018.


1999 ◽  
Author(s):  
Mark J. Eichler ◽  
Chi Hyun Kim ◽  
X. Edward Guo

Abstract The role of mechanical loading in trabecular bone adaptation is important for the understanding of bone integrity in different loading scenarios such as microgravity and for the etiology of age-related bone fractures. There have been numerous in vivo animal studies of bone adaptation, most of which are related to cortical bone remodeling, aimed at the investigation of Wolff’s Law [4], An interesting experimental model for trabecular bone adaptation has been developed in the rat tail vertebrae [2,3]. This model is attractive for trabecular bone adaptation studies because a controlled mechanical load can be applied to a whole vertebra with minimal surgical trauma, using a relatively inexpensive animal model. In addition, with advanced micro computed tomography (micro-CT) or micro magnetic resonance imaging (micro-MRI) coupled with large scale finite element modeling techniques, it is possible to characterize the three-dimensional (3D) stress/strain environment in the bone tissue close to a cellular level (∼25μm) [1]. Therefore, this in vivo rat tail model has a tremendous potential for quantification of the relationship between mechanical stimulation and biological response in trabecular bone adaptation.


2012 ◽  
Vol 134 (10) ◽  
Author(s):  
M. L. Roemhildt ◽  
B. D. Beynnon ◽  
M. Gardner-Morse ◽  
K. Anderson ◽  
G. J. Badger

This study describes the first application of a varus loading device (VLD) to the rat hind limb to study the role of sustained altered compressive loading and its relationship to the initiation of degenerative changes to the tibio-femoral joint. The VLD applies decreased compressive load to the lateral compartment and increased compressive load to the medial compartment of the tibio-femoral joint in a controlled manner. Mature rats were randomized into one of three groups: unoperated control, 0% (sham), or 80% body weight (BW). Devices were attached to an animal’s leg to deliver altered loads of 0% and 80% BW to the experimental knee for 12 weeks. Compartment-specific material properties of the tibial cartilage and subchondral bone were determined using indentation tests. Articular cartilage, calcified cartilage, and subchondral bone thicknesses, articular cartilage cellularity, and degeneration score were determined histologically. Joint tissues were sensitive to 12 weeks of decreased compressive loading in the lateral compartment with articular cartilage thickness decreased in the peripheral region, subchondral bone thickness increased, and cellularity of the midline region decreased in the 80% BW group as compared to the 0% BW group. The medial compartment revealed trends for diminished cellularity and aggregate modulus with increased loading. The rat-VLD model provides a new system to evaluate altered quantified levels of chronic in vivo loading without disruption of the joint capsule while maintaining full use of the knee. These results reveal a greater sensitivity of tissue parameters to decreased loading versus increased loading of 80% BW for 12 weeks in the rat. This model will allow future mechanistic studies that focus on the initiation and progression of degenerative changes with increased exposure in both magnitude and time to altered compressive loads.


Bone ◽  
2015 ◽  
Vol 81 ◽  
pp. 468-477 ◽  
Author(s):  
Zihui Li ◽  
Gisela Kuhn ◽  
Marcella von Salis-Soglio ◽  
Stephen J. Cooke ◽  
Michael Schirmer ◽  
...  

Author(s):  
W. J. Niessen ◽  
A. M. López ◽  
W. J. Enk ◽  
P. M. v. Roermund ◽  
B. M. ter Haar Romeny ◽  
...  

2006 ◽  
Vol 321-323 ◽  
pp. 278-281
Author(s):  
Wen Quan Cui ◽  
Ye Yeon Won ◽  
Myong Hyun Baek ◽  
Kwang Kyun Kim

The purpose of this study was to investigate the contribution of the microstructural properties of trabecular bone in predicting its elastic modulus in the intertrochanteric region. A total of 15 trabecular bone core specimens were obtained from the proximal femurs of patients undergoing total hip arthroplasty. The micro-computed tomography (micro-CT) was used to scan each specimen to obtain micro-morphology. Microstructural parameters were directly calculated using software. Micro-CT images were converted to micro-finite element model using meshing technique, and then micro-finite element analysis (FEA) was performed to assess the mechanical property (Young’s modulus) of trabecular bone. The results showed that the ability to explain this variance of Young’s modulus is improved by combining the structural indices with each other. It suggested that assessment of bone microarchitecture should be added as regards detection of osteoporosis and evaluation of the efficacy of drug treatments for osteoporosis.


2008 ◽  
Vol 27 (4) ◽  
pp. 854-859 ◽  
Author(s):  
Roland Krug ◽  
Julio Carballido-Gamio ◽  
Suchandrima Banerjee ◽  
Andrew J. Burghardt ◽  
Thomas M. Link ◽  
...  

2001 ◽  
Vol 91 (2) ◽  
pp. 912-918 ◽  
Author(s):  
Maria R. Moalli ◽  
Suquing Wang ◽  
Nancy J. Caldwell ◽  
Pravin V. Patil ◽  
Craig R. Maynard

Utilizing an in vivo model of trabecular bone formation, we demonstrated the temporal and spatial activation of pp125FAK in response to specific mechanical load stimuli. Bone chambers equipped with hydraulic actuators were aseptically inserted into each proximal tibial metaphysis of adult, male dogs under general anesthesia. The load stimulus consisted of a trapezoidal waveform, with a maximum compressive load of 17.8 N, loading rate of 89 N/s, at 1 Hz frequency. One chamber was loaded for 2 (120 cycles), 15 (900 cycles), or 30 min (1,800 cycles), whereas the contralateral chamber served as unloaded control. Bone chambers were biopsied at postload time points of 0, 15, and 45 min. Load-induced activation of FAK was rapid, and the duration of activation was dependent on the number of applied load cycles. Mechanical stimulation increased the association of FAK with Src and the time course of complex formation paralleled the temporal activation of FAK. Evaluation of cryosections revealed prominent FAK immunoreactivity among marrow fibroblasts and stromal cells.


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