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Chondroitin sulfate-E mediates estrogen-induced osteoanabolism.

Koike T, Mikami T, Shida M, Habuchi O, Kitagawa H - Sci Rep (2015)

Bottom Line: Here, we show that estrogen-induced, osteoanabolic effects were mediated via enhanced production of chondroitin sulfate-E (CS-E), which could act as an osteogenic stimulant in our cell-based system.Conversely, estrogen deficiency caused reduced expression of CS-E-synthesizing enzymes, including GalNAc4S-6ST, and led to decreased CS-E production in cultures of bone marrow cells derived from ovariectomized mice.Moreover, Galnac4s6st-deficient mice had abnormally low bone mass that resulted from impaired osteoblast differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.

ABSTRACT
Osteoporosis is an age-related disorder of bone remodeling in which bone resorption outstrips bone matrix deposition. Although anticatabolic agents are frequently used as first-line therapies for osteoporosis, alternative anabolic strategies that can enhance anabolic, osteogenic potential are actively sought. Sex steroid hormones, particularly estrogens, are bidirectional regulators for bone homeostasis; therefore, estrogen-mediated events are important potential targets for such anabolic therapies. Here, we show that estrogen-induced, osteoanabolic effects were mediated via enhanced production of chondroitin sulfate-E (CS-E), which could act as an osteogenic stimulant in our cell-based system. Conversely, estrogen deficiency caused reduced expression of CS-E-synthesizing enzymes, including GalNAc4S-6ST, and led to decreased CS-E production in cultures of bone marrow cells derived from ovariectomized mice. Moreover, Galnac4s6st-deficient mice had abnormally low bone mass that resulted from impaired osteoblast differentiation. These results indicated that strategies aimed at boosting CS-E biosynthesis are promising alternative therapies for osteoporosis.

No MeSH data available.


Related in: MedlinePlus

Osteopenic/osteoporotic phenotypes of Galnac4s6st−/− mice.(a,b) μCT analysis of tibias from 16-week-old male Galnac4s6st+/+ (WT), Galnac4s6st+/−, or Galnac4s6st−/− mice. μ-CT-derived measurement of BMD (a, n = 3 bones total, each from different litters). Data are represented as mean ± s.d. *, P < 0.05; **, P < 0.01, Tukey-Kramer test. Medial, longitudinal section through a μCT-generated three-dimensional reconstruction of a tibia (b). The cortical and trabecular regions are pseudo-colored light blue and yellow, respectively.
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f3: Osteopenic/osteoporotic phenotypes of Galnac4s6st−/− mice.(a,b) μCT analysis of tibias from 16-week-old male Galnac4s6st+/+ (WT), Galnac4s6st+/−, or Galnac4s6st−/− mice. μ-CT-derived measurement of BMD (a, n = 3 bones total, each from different litters). Data are represented as mean ± s.d. *, P < 0.05; **, P < 0.01, Tukey-Kramer test. Medial, longitudinal section through a μCT-generated three-dimensional reconstruction of a tibia (b). The cortical and trabecular regions are pseudo-colored light blue and yellow, respectively.

Mentions: At 16 weeks after birth, male Galnac4s6st−/− mice had significantly lower BMD than male wild-type (WT, Galnac4s6st+/+) littermates; a significant difference between Galnac4s6st+/− and Galnac4s6st+/+ littermates was also observed in the total BMD (Fig. 3a). Uniform decrease in BMD along the tibia of Galnac4s6st−/− mice indicated that both cortical and trabecular bones were affected equally (Supplementary Fig. S2). Using μCT three-dimensional reconstruction of tibias, we confirmed these observations (Fig. 3b). Thus, impaired synthesis of CS-E caused both cortical and trabecular bone loss in adult (at least 16-week-old), male mice.


Chondroitin sulfate-E mediates estrogen-induced osteoanabolism.

Koike T, Mikami T, Shida M, Habuchi O, Kitagawa H - Sci Rep (2015)

Osteopenic/osteoporotic phenotypes of Galnac4s6st−/− mice.(a,b) μCT analysis of tibias from 16-week-old male Galnac4s6st+/+ (WT), Galnac4s6st+/−, or Galnac4s6st−/− mice. μ-CT-derived measurement of BMD (a, n = 3 bones total, each from different litters). Data are represented as mean ± s.d. *, P < 0.05; **, P < 0.01, Tukey-Kramer test. Medial, longitudinal section through a μCT-generated three-dimensional reconstruction of a tibia (b). The cortical and trabecular regions are pseudo-colored light blue and yellow, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355730&req=5

f3: Osteopenic/osteoporotic phenotypes of Galnac4s6st−/− mice.(a,b) μCT analysis of tibias from 16-week-old male Galnac4s6st+/+ (WT), Galnac4s6st+/−, or Galnac4s6st−/− mice. μ-CT-derived measurement of BMD (a, n = 3 bones total, each from different litters). Data are represented as mean ± s.d. *, P < 0.05; **, P < 0.01, Tukey-Kramer test. Medial, longitudinal section through a μCT-generated three-dimensional reconstruction of a tibia (b). The cortical and trabecular regions are pseudo-colored light blue and yellow, respectively.
Mentions: At 16 weeks after birth, male Galnac4s6st−/− mice had significantly lower BMD than male wild-type (WT, Galnac4s6st+/+) littermates; a significant difference between Galnac4s6st+/− and Galnac4s6st+/+ littermates was also observed in the total BMD (Fig. 3a). Uniform decrease in BMD along the tibia of Galnac4s6st−/− mice indicated that both cortical and trabecular bones were affected equally (Supplementary Fig. S2). Using μCT three-dimensional reconstruction of tibias, we confirmed these observations (Fig. 3b). Thus, impaired synthesis of CS-E caused both cortical and trabecular bone loss in adult (at least 16-week-old), male mice.

Bottom Line: Here, we show that estrogen-induced, osteoanabolic effects were mediated via enhanced production of chondroitin sulfate-E (CS-E), which could act as an osteogenic stimulant in our cell-based system.Conversely, estrogen deficiency caused reduced expression of CS-E-synthesizing enzymes, including GalNAc4S-6ST, and led to decreased CS-E production in cultures of bone marrow cells derived from ovariectomized mice.Moreover, Galnac4s6st-deficient mice had abnormally low bone mass that resulted from impaired osteoblast differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.

ABSTRACT
Osteoporosis is an age-related disorder of bone remodeling in which bone resorption outstrips bone matrix deposition. Although anticatabolic agents are frequently used as first-line therapies for osteoporosis, alternative anabolic strategies that can enhance anabolic, osteogenic potential are actively sought. Sex steroid hormones, particularly estrogens, are bidirectional regulators for bone homeostasis; therefore, estrogen-mediated events are important potential targets for such anabolic therapies. Here, we show that estrogen-induced, osteoanabolic effects were mediated via enhanced production of chondroitin sulfate-E (CS-E), which could act as an osteogenic stimulant in our cell-based system. Conversely, estrogen deficiency caused reduced expression of CS-E-synthesizing enzymes, including GalNAc4S-6ST, and led to decreased CS-E production in cultures of bone marrow cells derived from ovariectomized mice. Moreover, Galnac4s6st-deficient mice had abnormally low bone mass that resulted from impaired osteoblast differentiation. These results indicated that strategies aimed at boosting CS-E biosynthesis are promising alternative therapies for osteoporosis.

No MeSH data available.


Related in: MedlinePlus