Tetracycline prevents cancellous bone loss and maintains near-normal rates of bone formation in streptozotocin diabetic rats

Bone ◽  
1997 ◽  
Vol 21 (2) ◽  
pp. 147-153 ◽  
Author(s):  
S. Bain ◽  
N.S. Ramamurthy ◽  
T. Impeduglia ◽  
S. Scolman ◽  
L.M. Golub ◽  
...  
2019 ◽  
Vol 20 (16) ◽  
pp. 3964 ◽  
Author(s):  
Wan Gong ◽  
Naidan Zhang ◽  
Gang Cheng ◽  
Quanlong Zhang ◽  
Yuqiong He ◽  
...  

Rehmanniae Radix Praeparata (RR, named as Shudihuang in traditional Chinese medicine), the steamed roots of Rehmannia glutinosa Libosch (Scrophulariaceae), has been demonstrated to have anti-diabetic and anti-osteoporotic activities. This study aimed to explore the protective effect and underlying mechanism of RR on diabetes-induced bone loss. It was found that RR regulated the alkaline phosphatase activity and osteocalcin level, enhanced bone mineral density, and improved the bone microarchitecture in diabetic rats. The catalpol (CAT), acteoside (ACT), and echinacoside (ECH) from RR increased the proliferation and differentiation of osteoblastic MC3T3-E1 cells injured by high glucose and promoted the production of IGF-1 and expression of related proteins in BMP and IGF-1/PI3K/mammalian target of rapamycin complex 1 (mTOR) signaling pathways. The verifying tests of inhibitors of BMP pathway (noggin) and IGF-1/PI3K/mTOR pathway (picropodophyllin) and molecular docking of IGF-1R further indicated that CAT, ACT, and ECH extracted from RR enhanced bone formation by regulating IGF-1/PI3K/mTOR signaling pathways. These findings suggest that RR may prove to be a promising candidate drug for the prevention and treatment of diabetes-induced osteoporosis.


2006 ◽  
Vol 85 (6) ◽  
pp. 510-514 ◽  
Author(s):  
R. Liu ◽  
H.S. Bal ◽  
T. Desta ◽  
N. Krothapalli ◽  
M. Alyassi ◽  
...  

Using a ligature-induced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated whether diabetes primarily affects periodontitis by enhancing bone loss or by limiting osseous repair. Diabetes increased the intensity and duration of the inflammatory infiltrate (P < 0.05). The formation of osteoclasts and percent eroded bone after 7 days of ligature placement was similar, while four days after removal of ligatures, the type 2 diabetic group had significantly higher osteoclast numbers and activity (P < 0.05). The amount of new bone formation following resorption was 2.4- to 2.9-fold higher in normoglycemic vs. diabetic rats (P < 0.05). Diabetes also increased apoptosis and decreased the number of bone-lining cells, osteoblasts, and periodontal ligament fibroblasts (P < 0.05). Thus, diabetes caused a more persistent inflammatory response, greater loss of attachment and more alveolar bone resorption, and impaired new bone formation. The latter may be affected by increased apoptosis of bone-lining and PDL cells.


1994 ◽  
Vol 267 (6) ◽  
pp. E853-E859 ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.


1995 ◽  
Vol 79 (6) ◽  
pp. 1889-1894 ◽  
Author(s):  
E. Zerath ◽  
F. Canon ◽  
C. Y. Guezennec ◽  
X. Holy ◽  
S. Renault ◽  
...  

Rat head-down hindlimb suspension (HS) has been shown to induce hindlimb cancellous bone loss. As HS is known to associate unloading with progressive disappearance of hindlimb muscle contractions, we investigated whether persisting muscle motion could modify suspension-induced bone disorders or even prevent them. Chronic electrical stimulation (ES) was applied to leg muscles of rats during 3-wk hindlimb suspension, the lack of support for hindlimbs maintaining a hypodynamic situation. The histomorphometric characteristics of the proximal tibial metaphysis were analyzed. At the end of this protocol of combined suspension and stimulation, trabecular bone loss remained similar to that of nonstimulated HS animals. However, trabecular bone cell activity parameters showed greater bone formation after muscle stimulation in unloaded animals, with significantly increased osteoblastic, osteoid, and mineralizing surfaces. In addition, periosteal mineral apposition rate and cancellous bone formation rate, markedly decreased by suspension, were not significantly different in suspended stimulated compared with normal loaded animals. This enhanced formation activity could be related to persistence of muscle activity, as shown by partial preservation of muscle mass. However, direct electrical effects on bone cannot be excluded. Thus, despite muscle stimulation, with enhanced bone formation, isolated suppression of hypokinesia has not been able to counteract bone effects of unloading. This finding supports the hypothesis of the importance of mechanical loading to maintain bone architecture.


2003 ◽  
Vol 95 (5) ◽  
pp. 1775-1780 ◽  
Author(s):  
T. E. Hefferan ◽  
G. L. Evans ◽  
S. Lotinun ◽  
M. Zhang ◽  
E. Morey-Holton ◽  
...  

Prologned spaceflight results in bone loss in astronauts, but there is considerable individual variation. The goal of this rat study was to determine whether gender influences bone loss during simulated weightlessness. Six-month-old Fisher 344 rats were hindlimb unweighted for 2 wk, after which the proximal tibiae were evaluated by histomorphometry. There were gender differences in tibia length, bone area, cancellous bone architecture, and bone formation. Compared with female rats, male rats had an 11.6% longer tibiae, a 27.8% greater cortical bone area, and a 37.6% greater trabecular separation. Conversely, female rats had greater cortical (316%) and cancellous (145%) bone formation rates, 28.6% more cancellous bone, and 30% greater trabecular number. Hindlimb unweighting resulted in large reductions in periosteal bone formation and mineral apposition rate in both genders. Unweighting also caused cancellous bone loss in both genders; trabecular number was decreased, and trabecular separation was increased. There was, however, no change in trabecular thickness in either gender. These architectural changes in cancellous bone were associated with decreases in bone formation and steady-state mRNA levels for bone matrix proteins and cancellous bone resorption. In conclusion, there are major gender-related differences in bone mass and turnover; however, the bone loss in hindlimb unweighted adult male and female rats appears to be due to similar mechanisms.


1995 ◽  
Vol 08 (04) ◽  
pp. 184-190
Author(s):  
A. R. Villanueva ◽  
M. R. Alvis ◽  
H. M. Aberman ◽  
A. S. Turner

SummaryA large animal model to study cancellous bone loss and the effect of various therapeutic agents following oestrogen deficiency-related bone loss is needed. Following double fluorochrome labeling at the time of surgery, six and 12 months later, static and dynamic histomorphometry was performed on undecalcified sections of the iliac crests of 16 mature (4 to 5-yearold) ewes following ovariectomy (OVX; n = 8) or sham-operation (Sham; n = 8). We found a slight decrease in bone mass associated with oestrogen deficiency as indicated by a statistically significant increase in trabecular separation (Tb.Sp: +14%, p <0.05) and decrease in wall thickness (W.Th: -10%, p <0.05) in the OVX group. However, at six months, we saw evidence of complete cessation of bone formation in both OVX and Sham animals. At that time there was a statistically significant (p <0.05) decline in the following parameters in both the Sham and OVX animals respectively: osteoid surface (OS: -79%, -77%), osteoid thickness (O.Th: -40%, -30%), flat osteoblasts (Fl.Ob.S: -87%, -94%), cuboidal osteoblasts (Cu.Ob.S: -88%, -65%), osteoid surface as a percentage of the total cancellous bone perimeter (OS/BS: -82%, -80%), osteoblast surface as a percentage of total cancellous bone surface (Ob.S/BS: -94%, -77%), mineralizing surface as a percentage of double labels plus half single labels (MS/OS: -44%, -42%), osteoid volume as a percentage of total area of mineralized bone plus osteoid (OV/TV: -88%, -88%), osteoid as a percentage of mineralized bone (OV/BV: -87%, -86%), osteoid maturation time (Omt: -27%, -35%), bone formation rate, surface referent (BFR/BS: -90%, -87%), bone formation rate, volume referent (BFR/BV: -89%, -86%), and bone formation rate, tissue referent (BFR/TV: -91%, -88%). The data was compared to static and dynamic histomorphometry of three intact ewes (similar age, breed, source) whose biopsies were taken two months after the second biopsies in the present study. The data indicate that there is a slight loss of trabecular bone following OVX but we are unable to explain the dramatic depression of bone turnover with little change in bone resorption. The data resembles the response seen when sheep are given daily doses of methylprednisolone. We speculate that this phenomenon may be a response to endogenous corticosteroid release in a response to stresses of transport, and surgery. A seasonal effect may be another explanation fro these changes, whereas dietary alteration (e. g. poisonous plants), hormonal changes or response to changes in physical activity are unlikely causes.A large animal model to study cancellous bone loss and effect of various therapeutic agents following oestrogen deficiency – related bone loss is needed. Following double fluorochrome labeling at the time of surgery, six and 12 months later, static and dynamic histomorphome-try was performed on undecal-cified sections of the iliac crests of 16 mature (4 to 5-year-old) ewes following ovariectomy (OVX; n = 8) or sham-operation (Sham; n = 8). A slight decrease in bone mass associated with oestrogen deficiency was seen but there was also evidence of complete cessation of bone formation in both OVX and Sham animals. The data resembles the responses seen when sheep are given daily doses of methylpednisolone and may be a response to endogenous corticosteroid release. A seasonal effect may be another explanation for these changes, whereas dietary alteration (e. g. poisonous plants), hormonal changes or response to changes in physical activity are unlikely causes.


2007 ◽  
Vol 53 (2) ◽  
pp. 190-195 ◽  
Author(s):  
Masayoshi Yamaguchi ◽  
Reiko Hamamoto ◽  
Satoshi Uchiyama ◽  
Kaori Ishiyama ◽  
Ken Hashimoto

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