J Korean Neurosurg Soc.  2020 Jul;63(4):433-443. 10.3340/jkns.2019.0097.

Rutin Improves Bone Histomorphometric Values by Reduction of Osteoclastic Activity in Osteoporosis Mouse Model Induced by Bilateral Ovariectomy

Affiliations
  • 1Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea
  • 2Department of Neurosurgery, Leon Wiltse Memorial Hospital, Suwon, Korea
  • 3Department of Neurosurgery, Chonnam National University Hospital, Gwangju, Korea

Abstract


Objective
: Osteoporosis is a disease of unbalanced bone metabolism that results in low bone mineral density with increased bone fragility and propensity for fractures. The increased rate of bone fracture due to osteoporosis places a significant burden on public health care expenditures. Therefore, numerous studies have been designed and performed to identify the drugs or health foods that can improve the bone quality or quantity. This study was designed to evaluate and analyze the therapeutic effects of rutin on histomorphometric values of the spine and femur in an osteoporotic mouse model induced by bilateral ovariectomy.
Methods
: Thirty female ICR mice (8 weeks old) underwent either a sham operation (only abdominal incision, sham group, n=10) or bilateral ovariectomy (n=20). The ovariectomized (OVX) animals were randomly divided into two groups : untreated OVX group (OVX-C, n=10), or rutin-administered group (OVX-R, n=10). The OVX-C group received weight-adjusted doses of saline vehicle and the OVX-R group received 50 mg/kg of rutin intraperitoneally, starting 1 day after surgery. At 4 and 8 weeks after surgery, serum estrogen, osteocalcin, alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX-1) were analyzed. Interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α were also analyzed. Bone histomorphometric parameters of the 4th lumbar vertebra and femur were determined by micro-computed tomography.
Results
: In OVX-C group, ALP, osteocalcin, CTX-1, IL-1β, IL-6, and TNF-α levels were significantly increased at 4 and 8 weeks compared to sham operation group. Rutin administration after OVX statistically significantly reduced ALP, CTX-1, IL-1β, IL-6, and TNF-α levels at 4 and 8 weeks. Rutin administration also improves bone histomorphometric parameters including trabecular bone volume fraction, trabecular thickness, and trabecular number. Trabecular separation was also decreased in OVX-R group compared to OVX-C group.
Conclusion
: The present study demonstrated that rutin has therapeutic effects on improving bone histomorphometric values in an OVX mouse model. The improvement in histomorphometric values may be associated with the reduction of osteoclastic activity via inhibition of IL-1β, IL-6, and TNF-α. In future studies, the mechanism for the effect of rutin on osteoporosis should be demonstrated more clearly to use rutin in human osteoporosis.

Keyword

Histomorphometric values; Mice; Osteoclast; Osteoporosis; Rutin

Figure

  • Fig. 1. Graph showing the changes of serum levels of estrogen (estradiol, E2). *p< 0.05 for the values of OVX-C or OVX-R group compared with that of sham group. † p<0.05 for the values of the OVX-C group compared with that of OVX-R group. OVX : ovariectomized, OVX-C : untreated OVX, OVX-R : rutin-administered.

  • Fig. 2. Graph showing the changes of serum levels of osteocalcin (A), ALP (B), and CTX-1 (C). *p< 0.05 for the values of OVX-C or OVX-R group compared with that of sham group. † p<0.05 for the values of the OVX-C group compared with that of OVX-R group. OVX : ovariectomized, OVX-C : untreated OVX, OVX-R : rutin-administered, ALP : alkaline phosphatase, CTX-1 : type I collagen C-terminus.

  • Fig. 3. Graph showing the changes of serum levels of IL-1β (A), IL-6 (B), and TNF-α (C). *p< 0.05 for the values of OVX-C or OVX-R group compared with that of sham group. † p<0.05 for the values of the OVX-C group compared with that of OVX-R group. OVX : ovariectomized, OVX-C : untreated OVX, OVX-R : rutin-administered, IL : interleukin, TNF : tumor necrosis factor.

  • Fig. 4. Bar graph showing the result of histomorphometric analyses of 4th lumbar vertebrae in the sham, OVX-C and OVX-R group : BV/TV (A), Tb.Th. (B), Tb.N. (C), and Tb.S. (D). *p< 0.05 for the values of OVX-C or OVX-R group compared with that of sham group. † p<0.05 for the values of the OVX-C group compared with that of OVX-R group. OVX : ovariectomized, OVX-C : untreated OVX, OVX-R : rutin-administered, BV/TV : trabecular bone volume fraction, Tb.Th. : trabecular thickness, Tb.N. : trabecular number, Tb.S. : trabecular separation.

  • Fig. 5. Bar graph showing the result of histomorphometric analyses of femur in the sham, OVX-C and OVX-R group : BV/TV (A), Tb.Th. (B), Tb.N. (C), and Tb.S. (D). *p< 0.05 for the values of OVX-C or OVX-R group compared with that of sham group. † p<0.05 for the values of the OVX-C group compared with that of OVX-R group. OVX : ovariectomized, OVX-C : untreated OVX, OVX-R : rutin-administered, BV/TV : trabecular bone volume fraction, Tb.Th. : trabecular thickness, Tb.N. : trabecular number, Tb.S. : trabecular separation.

  • Fig. 6. Representative micro computed tomography (CT) images of the 4th lumbar vertebrae in the sham, OVX-C, and OVX-R groups : 4 weeks (A) and 8 weeks (B) reconstruction images. OVX : ovariectomized, OVX-C : untreated OVX, OVX-R : rutin-administered.


Reference

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