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Chondrocytes-Specific Expression of Osteoprotegerin Modulates Osteoclast Formation in Metaphyseal Bone.

Wang B, Jin H, Shu B, Mira RR, Chen D - Sci Rep (2015)

Bottom Line: TRAP staining showed that osteoclast numbers were reduced in both secondary ossification center and proximal metaphysis.In contrast, the mineral apposition rates were not changed in Col2-Opg transgenic mice.Our results demonstrated that OPG expression in chondrocyte increases bone mass in the proximal metaphysis of tibiae through negative regulation of osteoclast formation.

View Article: PubMed Central - PubMed

Affiliation: Key Lab of Hormone and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.

ABSTRACT
Bone marrow stromal cells/osteoblasts were originally thought to be the major player in regulating osteoclast differentiation through expressing RANKL/OPG cytokines. Recent studies have established that chondrocytes also express RANKL/OPG and support osteoclast formation. Till now, the in vivo function of chondrocyte-produced OPG in osteoclast formation and postnatal bone growth has not been directly investigated. In this study, chondrocyte-specific Opg transgenic mice were generated by using type II collagen promoter. The Col2-Opg transgenic mice showed delayed formation of secondary ossification center and localized increase of bone mass in proximal metaphysis of tibiae. TRAP staining showed that osteoclast numbers were reduced in both secondary ossification center and proximal metaphysis. This finding was further confirmed by in vitro chondrocyte/spleen cell co-culture assay. In contrast, the mineral apposition rates were not changed in Col2-Opg transgenic mice. TUNEL staining revealed more apoptotic hypertrophic chondrocytes in the growth plate of Col2-Opg mice. Flow cytometry analysis showed fewer RANK-expressing cells in the marrow of Col2a1-Opg mice, suggesting the role of OPG in blocking the differentiation of early mesenchymal progenitors into RANK-expressing pre-osteoclasts. Our results demonstrated that OPG expression in chondrocyte increases bone mass in the proximal metaphysis of tibiae through negative regulation of osteoclast formation.

No MeSH data available.


Related in: MedlinePlus

μCT analysis of the bone mass of Col2-Opg mice.(A) μCT analysis of bone mass of the proximal metaphysis of tibiae was examined in 4-week-old Col2-Opg mice and WT littermates. (B–G) Histomorphometric parameters, including bone volume (BV/TV, %), bone mineral density (BMD), trabecular number (Tb.N.), connectivity density (Conn. D.), trabecular separation (Tb.Sp.), and structure model index (SMI), were analyzed in Col2-Opg mice and WT littermates. Data are represented as means ± SD (n = 6 per group).
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f3: μCT analysis of the bone mass of Col2-Opg mice.(A) μCT analysis of bone mass of the proximal metaphysis of tibiae was examined in 4-week-old Col2-Opg mice and WT littermates. (B–G) Histomorphometric parameters, including bone volume (BV/TV, %), bone mineral density (BMD), trabecular number (Tb.N.), connectivity density (Conn. D.), trabecular separation (Tb.Sp.), and structure model index (SMI), were analyzed in Col2-Opg mice and WT littermates. Data are represented as means ± SD (n = 6 per group).

Mentions: Consistent with this, μCT imaging revealed the bone mass increase in the proximal metaphysis beneath the growth plate in 4-week-old Col2-Opg mice (Fig. 3A). The trabecular bone volume (% BV/TV) was 41% greater (Fig. 3B) and the bone mineral density was 29% greater (Fig. 3C) in Col2-Opg mice. The trabecular number (Tb. N., 1/mm) was 20% higher (Fig. 3D), and the connectivity density (Conn. D.) was 60% higher (Fig. 3E), while the trabecular separation (Tb.Sp.) was 24% lower (Fig. 3F) in Col2-Opg mice. The structural model index (SMI, a measure of the shape of trabeculae; 0 for plates and 3 for cylindrical rods) was significantly decreased by 21% in Col2-Opg mice (Fig. 3G).


Chondrocytes-Specific Expression of Osteoprotegerin Modulates Osteoclast Formation in Metaphyseal Bone.

Wang B, Jin H, Shu B, Mira RR, Chen D - Sci Rep (2015)

μCT analysis of the bone mass of Col2-Opg mice.(A) μCT analysis of bone mass of the proximal metaphysis of tibiae was examined in 4-week-old Col2-Opg mice and WT littermates. (B–G) Histomorphometric parameters, including bone volume (BV/TV, %), bone mineral density (BMD), trabecular number (Tb.N.), connectivity density (Conn. D.), trabecular separation (Tb.Sp.), and structure model index (SMI), were analyzed in Col2-Opg mice and WT littermates. Data are represented as means ± SD (n = 6 per group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556963&req=5

f3: μCT analysis of the bone mass of Col2-Opg mice.(A) μCT analysis of bone mass of the proximal metaphysis of tibiae was examined in 4-week-old Col2-Opg mice and WT littermates. (B–G) Histomorphometric parameters, including bone volume (BV/TV, %), bone mineral density (BMD), trabecular number (Tb.N.), connectivity density (Conn. D.), trabecular separation (Tb.Sp.), and structure model index (SMI), were analyzed in Col2-Opg mice and WT littermates. Data are represented as means ± SD (n = 6 per group).
Mentions: Consistent with this, μCT imaging revealed the bone mass increase in the proximal metaphysis beneath the growth plate in 4-week-old Col2-Opg mice (Fig. 3A). The trabecular bone volume (% BV/TV) was 41% greater (Fig. 3B) and the bone mineral density was 29% greater (Fig. 3C) in Col2-Opg mice. The trabecular number (Tb. N., 1/mm) was 20% higher (Fig. 3D), and the connectivity density (Conn. D.) was 60% higher (Fig. 3E), while the trabecular separation (Tb.Sp.) was 24% lower (Fig. 3F) in Col2-Opg mice. The structural model index (SMI, a measure of the shape of trabeculae; 0 for plates and 3 for cylindrical rods) was significantly decreased by 21% in Col2-Opg mice (Fig. 3G).

Bottom Line: TRAP staining showed that osteoclast numbers were reduced in both secondary ossification center and proximal metaphysis.In contrast, the mineral apposition rates were not changed in Col2-Opg transgenic mice.Our results demonstrated that OPG expression in chondrocyte increases bone mass in the proximal metaphysis of tibiae through negative regulation of osteoclast formation.

View Article: PubMed Central - PubMed

Affiliation: Key Lab of Hormone and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.

ABSTRACT
Bone marrow stromal cells/osteoblasts were originally thought to be the major player in regulating osteoclast differentiation through expressing RANKL/OPG cytokines. Recent studies have established that chondrocytes also express RANKL/OPG and support osteoclast formation. Till now, the in vivo function of chondrocyte-produced OPG in osteoclast formation and postnatal bone growth has not been directly investigated. In this study, chondrocyte-specific Opg transgenic mice were generated by using type II collagen promoter. The Col2-Opg transgenic mice showed delayed formation of secondary ossification center and localized increase of bone mass in proximal metaphysis of tibiae. TRAP staining showed that osteoclast numbers were reduced in both secondary ossification center and proximal metaphysis. This finding was further confirmed by in vitro chondrocyte/spleen cell co-culture assay. In contrast, the mineral apposition rates were not changed in Col2-Opg transgenic mice. TUNEL staining revealed more apoptotic hypertrophic chondrocytes in the growth plate of Col2-Opg mice. Flow cytometry analysis showed fewer RANK-expressing cells in the marrow of Col2a1-Opg mice, suggesting the role of OPG in blocking the differentiation of early mesenchymal progenitors into RANK-expressing pre-osteoclasts. Our results demonstrated that OPG expression in chondrocyte increases bone mass in the proximal metaphysis of tibiae through negative regulation of osteoclast formation.

No MeSH data available.


Related in: MedlinePlus