Recovery periods restore mechanosensitivity to dynamically loaded bone

2001 ◽  
Vol 204 (19) ◽  
pp. 3389-3399 ◽  
Author(s):  
Alexander G. Robling ◽  
David B. Burr ◽  
Charles H. Turner
Keyword(s):  
Bone Formation ◽  
Bone Cells ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Four Point Bending ◽  
Rat Tibia ◽  
Time Required ◽  
The Right

SUMMARY Bone cells are capable of sensing and responding to mechanical forces, but mechanosensitivity begins to decline soon after the stimulus is initiated. Under continued stimulation, bone is desensitized to mechanical stimuli. We sought to determine the amount of time required to restore mechanosensitivity to desensitized bone cells in vivo by manipulating the recovery time (0, 0.5, 1, 2, 4 or 8 h) allowed between four identical daily loading bouts. We also investigated the osteogenic effectiveness of shorter-term recovery periods, lasting several seconds (0.5, 3.5, 7 or 14 s), introduced between each of 36 identical daily loading cycles. Using the rat tibia four-point bending model, the right tibia of 144 adult female Sprague-Dawley rats was subjected to bending, sham bending or no loading. In the rats receiving recovery periods between loading bouts, histomorphometric measurements from the endocortical surface of the loaded and nonloaded control (left) tibiae revealed more than 100 % higher relative bone formation rates in the 8 h recovery group than in the 0 and 0.5 h recovery groups. Approximately 8 h of recovery was sufficient to restore full mechanosensitivity to the cells. In the rats allowed time to recover between load cycles, 14 s of recovery resulted in significantly higher (66–190 %) relative bone formation rates compared to any of the three shorter recovery periods. In both experiments, bone formation in the sham-bending animals was similar to that in the nonloaded control group. The results demonstrate the importance of recovery periods for (i) restoring mechanosensitivity to bone cells and (ii) maximizing the osteogenic effects of mechanical loading (exercise) regimens.

scholarly journals How does intraarticular dexmedetomidine injection effect articular cartilage and synovium? An animal study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Başak Akça ◽  
Aysun Ankay Yılbaş ◽  
Filiz Üzümcügil ◽  
Berkem Büyükakkuş ◽  
Elham Bahador Zırh ◽  
...  
Keyword(s):  
Pain Relief ◽  
Knee Joint ◽  
Animal Study ◽  
Left Knee ◽  
Control Group ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Arthroscopic Knee ◽  
The Right

Abstract Background Intraarticular injections are widely used to provide pain relief after arthroscopic procedures and minimize the use of opioids. Dexmedetomidine has been proven to potentiate pain relief and postpone the demand for the first analgesic drug when it is used intraarticularly following arthroscopic knee procedures. However, the effects of dexmedetomidine on articular structures have not yet been evaluated. Our aim was to determine the effects of intraarticular dexmedetomidine injection on articular structures such as cartilage and synovium. Design Animal study. Methods Twenty adult rats (Sprague-Dawley) were enrolled in the study. Following appropriate aseptic and anesthetic conditions, dexmedetomidine (100 mcg/ml) (0.25 ml) was injected into the right knee joint (the study group) and normal saline solution (0.25 ml) into the left knee joint (the control group) of the rats. Four rats were sacrificed from each group on days 1, 2, 7, 14, and 21, and knee joint samples were obtained. Histologists evaluated the articular and periarticular regions and the synovium using histological sections, and a five-point scale was used to grade the inflammatory changes in a blinded manner. Results The groups were found to be similar in terms of median congestion scores, edema and inflammation scores, subintimal fibrosis, neutrophil activation and cartilage structure at each of the time intervals. Conclusion In our placebo-controlled, in vivo trial, the intraarticular use of dexmedetomidine seemed to be safe with respect to the studied histopathological parameters. However, complementary studies investigating the histopathological effects, analgesic dosage and adverse effects of dexmedetomidine on damaged articular structure models are needed.

scholarly journals Thermally induced osteocyte damage initiates pro-osteoclastogenic gene expression in vivo

2016 ◽  
Vol 13 (119) ◽  
pp. 20160337 ◽  
Author(s):  
Eimear B. Dolan ◽  
David Tallon ◽  
Wing-Yee Cheung ◽  
Mitchell B. Schaffler ◽  
Oran D. Kennedy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thermal Damage ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Cellular Damage ◽  
Sprague Dawley ◽  
Related Factors ◽  
Thermally Induced ◽  
Rat Tibia

Bone is often subject to harsh temperatures during orthopaedic procedures resulting in thermally induced bone damage, which may affect the healing response. Postsurgical healing of bone is essential to the success of surgery, therefore, an understanding of the thermally induced responses of bone cells to clinically relevant temperatures in vivo is required. Osteocytes have been shown to be integrally involved in the bone remodelling cascade, via apoptosis, in micro-damage systems. However, it is unknown whether this relationship is similar following thermal damage. Sprague–Dawley rat tibia were exposed to clinically relevant temperatures (47°C or 60°C) to investigate the role of osteocytes in modulating remodelling related factors. Immunohistochemistry was used to quantify osteocyte thermal damage (activated caspase-3). Thermally induced pro-osteoclastogenic genes ( Rankl , Opg and M-csf ), in addition to genes known to mediate osteoblast and osteoclast differentiation via prostaglandin production ( Cox2 ), vascularization ( Vegf ) and inflammatory ( Il1a ) responses, were investigated using gene expression analysis. The results demonstrate that heat-treatment induced significant bone tissue and cellular damage. Pro-osteoclastogenic genes were upregulated depending on the amount of temperature elevation compared with the control. Taken together, the results of this study demonstrate the in vivo effect of thermally induced osteocyte damage on the gene expression profile.

Facilitated migration of cells from a transected peripheral nerve over collagen fibers: in vivo observations

1989 ◽  
Vol 47 ◽  
pp. 888-889
Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Collagen Gel ◽  
Collagen Fibers ◽  
Control Group ◽  
Guide Tube ◽  
Sprague Dawley ◽  
Silicone Tube ◽  
Thin Sections

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.

scholarly journals Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics

2021 ◽  
Vol 14 (4) ◽  
pp. 289
Author(s):  
Sana Ansari ◽  
Bregje W. M. de de Wildt ◽  
Michelle A. M. Vis ◽  
Carolina E. de de Korte ◽  
Keita Ito ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Cells ◽  
Bone Mineralization ◽  
Recipient Cell ◽  
Organic Matrix ◽  
Matrix Vesicles ◽  
Matrix Mineralization

Bone is a complex organ maintained by three main cell types: osteoblasts, osteoclasts, and osteocytes. During bone formation, osteoblasts deposit a mineralized organic matrix. Evidence shows that bone cells release extracellular vesicles (EVs): nano-sized bilayer vesicles, which are involved in intercellular communication by delivering their cargoes through protein–ligand interactions or fusion to the plasma membrane of the recipient cell. Osteoblasts shed a subset of EVs known as matrix vesicles (MtVs), which contain phosphatases, calcium, and inorganic phosphate. These vesicles are believed to have a major role in matrix mineralization, and they feature bone-targeting and osteo-inductive properties. Understanding their contribution in bone formation and mineralization could help to target bone pathologies or bone regeneration using novel approaches such as stimulating MtV secretion in vivo, or the administration of in vitro or biomimetically produced MtVs. This review attempts to discuss the role of MtVs in biomineralization and their potential application for bone pathologies and bone regeneration.

Characterization of in vivo strain in the rat tibia during external application of a four-point bending load

1992 ◽  
Vol 25 (10) ◽  
pp. 1241-1246 ◽  
Author(s):  
M.P. Akhter ◽  
D.M. Raab ◽  
C.H. Turner ◽  
D.B. Kimmel ◽  
R.R. Recker
Keyword(s):  
External Application ◽  
Four Point Bending ◽  
Bending Load ◽  
Rat Tibia

Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat

1998 ◽  
Vol 275 (5) ◽  
pp. R1468-R1477 ◽  
Author(s):  
Scott K. Powers ◽  
Haydar A. Demirel ◽  
Heather K. Vincent ◽  
Jeff S. Coombes ◽  
Hisashi Naito ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Control Group ◽  
Sprague Dawley ◽  
Endurance Exercise Training ◽  
Nonprotein Thiols

Experimental studies examining the effects of regular exercise on cardiac responses to ischemia and reperfusion (I/R) are limited. Therefore, these experiments examined the effects of endurance exercise training on myocardial biochemical and physiological responses during in vivo I/R. Female Sprague-Dawley rats (4 mo old) were randomly assigned to either a sedentary control group or to an exercise training group. After a 10-wk endurance exercise training program, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 20 min, followed by a 10-min period of reperfusion. Compared with untrained, exercise-trained animals maintained higher ( P < 0.05) peak systolic blood pressure throughout I/R. Training resulted in a significant ( P < 0.05) increase in ventricular nonprotein thiols, heat shock protein (HSP) 72, and the activities of superoxide dismutase (SOD), phosphofructokinase (PFK), and lactate dehydrogenase. Furthermore, compared with untrained controls, left ventricles from trained animals exhibited lower levels ( P < 0.05) of lipid peroxidation after I/R. These data demonstrate that endurance exercise training improves myocardial contractile performance and reduces lipid peroxidation during I/R in the rat in vivo. It appears likely that the improvement in the myocardial responses to I/R was related to training-induced increases in nonprotein thiols, HSP72, and the activities of SOD and PFK in the myocardium.

scholarly journals Contralateral spreading of substances following intratympanic nanoparticle-conjugated gentamicin injection in a rat model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sang-Yeon Lee ◽  
Jeonghyo Kim ◽  
Sangjin Oh ◽  
Gaon Jung ◽  
Ki-Jae Jeong ◽  
...  
Keyword(s):  
Eustachian Tube ◽  
Rat Model ◽  
Control Group ◽  
Fluorescent Nanoparticles ◽  
Sprague Dawley ◽  
Surface Charges ◽  
Cochlear Hair Cells ◽  
Intratympanic Injection ◽  
Group 2 ◽  
The Right

Abstract This study was performed to investigate the Eustachian tube as a potential route for contralateral spreading following intratympanic nanoparticle (NP)-conjugated gentamicin injection in a rat model. Sprague–Dawley rats were divided into three groups and substances were injected in the right ear: group 1 (fluorescent magnetic nanoparticles [F-MNPs], n = 4), group 2 (F-MNP-conjugated gentamicin [F-MNP@GM], n = 2), and control group (no injections, n = 2). T2-weighted sequences corresponding to the regions of interest at 1, 2, and 3 h after intratympanic injection were evaluated, along with immunostaining fluorescence of both side cochlea. The heterogeneous signal intensity of F-MNPs and F-MNP@GM on T2-weighted images, observed in the ipsilateral tympanum, was also detected in the contralateral tympanum in 4 out of 6 rats, recapitulating fluorescent nanoparticles in the contralateral cochlear hair cells. Computational simulations demonstrate the contralateral spreading of particles by gravity force following intratympanic injection in a rat model. The diffusion rate of the contralateral spreading relies on the sizes and surface charges of particles. Collectively, the Eustachian tube could be a route for contralateral spreading following intratympanic injection. Caution should be taken when using the contralateral ear as a control study investigating inner-ear drug delivery through the transtympanic approach.

Dexmedetomidine elevates the lethal dose threshold of bupivacaine in rats: A dosing study

2019 ◽  
Vol 39 (3) ◽  
pp. 365-373
Author(s):  
L Pan ◽  
Y Zhang ◽  
Y He ◽  
Z Chen ◽  
S Wang ◽  
...  
Keyword(s):  
Femoral Vein ◽  
Lethal Dose ◽  
Control Group ◽  
Sprague Dawley ◽  
Dose Threshold ◽  
Sd Rats ◽  
Group 12 ◽  
Group 3 ◽  
The Right ◽  
Group 1

Dexmedetomidine (DMED), an alpha-2 adrenoreceptor agonist, has been widely used in regional anesthesia procedures. However, the effect of DMED on local anesthetic cardiotoxicity has not been well delineated. This study consisted of two experiments. In experiment A, 42 Sprague–Dawley (SD) rats were randomly divided into 6 groups ( n = 7), each group was pretreated with DMED 0 μg kg−1 (D0 group), 1 μg kg−1 (D1 group), 3 μg kg−1 (D3 group), 6 μg kg−1 (D6 group), 12 μg kg−1 (D12 group), and 24 μg kg−1 (D24 group), administered through the right femoral vein. In experiment B, 20 SD rats were randomly divided into 4 groups ( n = 5), such as control group, DMED group, yohimbine (YOH) group, and DMED + YOH group. Each subgroup in experiment B was also pretreated similarly as in experiment A. After pretreatment of rats as described above (in experiments A and B), bupivacaine 2.5 mg kg−1 min−1 was infused to induce cardiac arrest. In experiment A, the lethal dose threshold of bupivacaine and plasma bupivacaine concentration in D3 and D6 group were higher than the other groups. In experiment B, there was no interaction between DMED and YOH in lethal dose threshold, arrhythmia time, plasma concentration of bupivacaine, and myocardial content of bupivacaine. DMED doses of 3–6 μg kg−1 elevated the lethal dose threshold of bupivacaine without involvement of the alpha-2 adrenoceptors.

Buprenorphine alleviation of pain does not compromise the rat monoarthritic pain model

2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
M.S. Berke ◽  
Klas S.P. Abelson
Keyword(s):  
Rat Model ◽  
Joint Stiffness ◽  
Positive Control ◽  
Negative Control ◽  
Pain Tolerance ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
A Minor

Abstract Aims This study investigated the effects of buprenorphine treatment on pain and welfare parameters and model specific parameters in a rat model of monoarthritis to eliminate unnecessary pain from this model. Methods 32 male Sprague Dawley rats were divided into four groups: (1) A negative control without arthritis receiving no analgesia. (2) A positive monoarthritic control group receiving no analgesia, but subcutaneous saline injections twice a day. (3) A positive control with monoarthritis receiving subcutaneous carprofen once a day and saline once a day. (4) A group with monoarthritis receiving subcutaneous buprenorphine twice a day. Monoarthritis was induced with an injection of 0.02 ml Complete Freund’s Adjuvant intra-articularly in the left tibiotarsal joint. Treatment with analgesia was initiated at day 15 and the rats were euthanized at day 23. Results The induced monoarthritis elicited a pronounced acute inflammation. Several parameters such as bodyweight, mobility, stance, joint-stiffness and lameness scores were affected. A marked mechanical hyperalgesia in the tarsal area was observed by Electronic Von Frey testing, but no severe compromise of the animal welfare was seen at any time. Signs of chronic development began to appear from day 10 after the monoarthritic induction. No significant change in serum cytokines and faecal corticosterone measurements was found after administration of buprenorphine. A minor decrease in body weight was seen, and a higher pain tolerance to mechanical stimuli was observed, indicating pain alleviation. The histological examination confirmed monoarthritic development in all monoarthritic rats and revealed periarticular lesions suggesting diffusion of adjuvant from intra-articular injection site to the periphery. Conclusions The study demonstrated that buprenorphine has an analgesic effect in the adjuvant induced monoarthritic rat model, without obvious interference with the development of arthritis.

scholarly journals BONE INDUCTION BY BMP-2 EXPRESSING ADENOVIRAL VECTOR IN RATS UNDER TREATMENT WITH FK506

2002 ◽  
Vol 06 (01) ◽  
pp. 23-29 ◽  
Author(s):  
Junya Sonobe ◽  
Kazuhisa Bessho ◽  
Shinji Kaihara ◽  
Yasunori Okubo ◽  
Tadahiko Iizuka
Keyword(s):  
Adenoviral Vector ◽  
Host Immunity ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Group Iii ◽  
Group I ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
The Right

The purpose of this study was to investigate the effectiveness of human bone morphogenetic protein-2 (BMP-2) expressing adenoviral vector in vivo. The day before vector injection, immunosuppressant FK506 was given subcutaneously to each rat at doses of 12 mg/kg (Group I), 6 mg/kg (Group II) and 3 mg/kg (Group III). FK506 was not administered to the six rats of the control group. Twenty-five liters of AXCAOBMP-2 (3.93 × 109pfu/ml) were injected into the right calf muscle of all rats. On day 21 after vector injection, all groups were investigated radiologically, histologically, and biochemically. Osteoinduction was seen in the AxCAOBMP-2-injected groups with immunosuppression. However, no bone formation was observed in the control group. These findings suggest that AxCAOBMP-2 has the potential of osteoinduction under transient immunosuppression. AxCAOBMP-2 may be useful for future clinical application in bone reconstruction, if host immunity response can be regulated.

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