Limits...
Osteoblast recruitment and bone formation enhanced by cell matrix-associated heparin-binding growth-associated molecule (HB-GAM).

Imai S, Kaksonen M, Raulo E, Kinnunen T, Fages C, Meng X, Lakso M, Rauvala H - J. Cell Biol. (1998)

Bottom Line: We show here that heparin-binding growth-associated molecule (HB-GAM), an extracellular matrix-associated protein that enhances migratory responses in neurons, is prominently expressed in the cell matrices that act as target substrates for bone formation.The HB-GAM transgenic mice develop a phenotype characterized by an increased bone thickness.HB-GAM may thus play an important role in bone formation, probably by mediating recruitment and attachment of osteoblasts/osteoblast precursors to the appropriate substrates for deposition of new bone.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Shiga University of Medical Science, Shiga-ken, 520-2192, Japan. simai@belle.shiga-med.ac.jp

ABSTRACT
Bone has an enormous capacity for growth, regeneration, and remodeling. This capacity is largely due to induction of osteoblasts that are recruited to the site of bone formation. The recruitment of osteoblasts has not been fully elucidated, though the immediate environment of the cells is likely to play a role via cell- matrix interactions. We show here that heparin-binding growth-associated molecule (HB-GAM), an extracellular matrix-associated protein that enhances migratory responses in neurons, is prominently expressed in the cell matrices that act as target substrates for bone formation. Intriguingly, N-syndecan, which acts as a receptor for HB-GAM, is expressed by osteoblasts/osteoblast precursors, whose ultrastructural phenotypes suggest active cell motility. The hypothesis that HB-GAM/N-syndecan interaction mediates osteoblast recruitment, as inferred from developmental studies, was tested using osteoblast-type cells that express N-syndecan abundantly. These cells migrate rapidly to HB-GAM in a haptotactic transfilter assay and in a migration assay where HB-GAM patterns were created on culture wells. The mechanism of migration is similar to that previously described for the HB-GAM-induced migratory response of neurons. Our hypothesis that HB-GAM/N-syndecan interaction participates in regulation of osteoblast recruitment was tested using two different in vivo models: an adjuvant-induced arthritic model and a transgenic model. In the adjuvant-induced injury model, the expression of HB-GAM and of N-syndecan is strongly upregulated in the periosteum accompanying the regenerative response of bone. In the transgenic model, the HB-GAM expression is maintained in mesenchymal tissues with the highest expression in the periosteum. The HB-GAM transgenic mice develop a phenotype characterized by an increased bone thickness. HB-GAM may thus play an important role in bone formation, probably by mediating recruitment and attachment of osteoblasts/osteoblast precursors to the appropriate substrates for deposition of new bone.

Show MeSH

Related in: MedlinePlus

Electron-microscopic characterization of  N-syndecan–expressing cells.  (a) N-syndecan is not expressed by any cell types of  the healthy adult bone (oc,  osteocyte; ob, osteoblasts; fb,  fibroblast-like cell). (b) N-syndecan is not expressed by the  cellular components along  the bone surface of 7 d after  adjuvant inoculation (day 7).  The bone surface is characterized by numerous spindle-shaped small cells (diameter = 2–3 μm; double  arrowheads), cell processes  of these cells (arrowheads),  and long cell processes extending from the osteocytes  (arrow). (c) N-syndecan is  detected for the first time at  day 10 (arrows). N-syndecan  is expressed on the spindle-shaped small cells (arrow, diameter of the cells = 2–3  μm) and on their long slender cell processes (double arrowheads). (d) N-syndecan  is expressed (arrow) by the  osteoblast-like cells (ob-l)  characterized by cuboid-shaped large cell soma (diameter = 8–12 μm), rich  rough ER (+), and Golgi apparatus (asterisk) at day 14.  (e) N-syndecan expression  remaining on the cell surface  of osteocyte-like cells (oc-l)  characterized by lens-shaped  small cell soma at day 21 (diameter of the cells = 3–4  μm). These cells have not yet developed gap junctions with the neighboring cells (asterisk), a typical feature of fully differentiated osteocytes. (f) N-syndecan is not expressed by the fully differentiated osteocytes characterized by satellite-shaped cell soma with the cell processes radiating into the mineralized bone matrix at day 28 (arrows). The rectangles in c–e indicate the insets. Bars: (a) 4 μm; (b) 2.3 μm;  (c) 2 μm; (d) 1.9 μm; (e) 2.6 μm; (f) 3.2 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2132954&req=5

Figure 6: Electron-microscopic characterization of N-syndecan–expressing cells. (a) N-syndecan is not expressed by any cell types of the healthy adult bone (oc, osteocyte; ob, osteoblasts; fb, fibroblast-like cell). (b) N-syndecan is not expressed by the cellular components along the bone surface of 7 d after adjuvant inoculation (day 7). The bone surface is characterized by numerous spindle-shaped small cells (diameter = 2–3 μm; double arrowheads), cell processes of these cells (arrowheads), and long cell processes extending from the osteocytes (arrow). (c) N-syndecan is detected for the first time at day 10 (arrows). N-syndecan is expressed on the spindle-shaped small cells (arrow, diameter of the cells = 2–3 μm) and on their long slender cell processes (double arrowheads). (d) N-syndecan is expressed (arrow) by the osteoblast-like cells (ob-l) characterized by cuboid-shaped large cell soma (diameter = 8–12 μm), rich rough ER (+), and Golgi apparatus (asterisk) at day 14. (e) N-syndecan expression remaining on the cell surface of osteocyte-like cells (oc-l) characterized by lens-shaped small cell soma at day 21 (diameter of the cells = 3–4 μm). These cells have not yet developed gap junctions with the neighboring cells (asterisk), a typical feature of fully differentiated osteocytes. (f) N-syndecan is not expressed by the fully differentiated osteocytes characterized by satellite-shaped cell soma with the cell processes radiating into the mineralized bone matrix at day 28 (arrows). The rectangles in c–e indicate the insets. Bars: (a) 4 μm; (b) 2.3 μm; (c) 2 μm; (d) 1.9 μm; (e) 2.6 μm; (f) 3.2 μm.

Mentions: To identify the cell types that express N-syndecan during the adult periosteal ossification, a detailed electron-microscopical study was performed. Fully differentiated osteoblasts covering the surface of healthy adult bone (Fig. 5 c, rectangle) did not express N-syndecan (Fig. 6 a). Interestingly, the osteoblasts were not found on the surface of the damaged bone 7 d after adjuvant inoculation (day 7; Fig. 5 f, rectangle). Instead, numerous spindle-shaped cells and their cell processes, which may represent fibroblastic osteoprogenitor, were noted along the bone surface. However, these cells were not immunoreactive to N-syndecan (Fig. 6 b).


Osteoblast recruitment and bone formation enhanced by cell matrix-associated heparin-binding growth-associated molecule (HB-GAM).

Imai S, Kaksonen M, Raulo E, Kinnunen T, Fages C, Meng X, Lakso M, Rauvala H - J. Cell Biol. (1998)

Electron-microscopic characterization of  N-syndecan–expressing cells.  (a) N-syndecan is not expressed by any cell types of  the healthy adult bone (oc,  osteocyte; ob, osteoblasts; fb,  fibroblast-like cell). (b) N-syndecan is not expressed by the  cellular components along  the bone surface of 7 d after  adjuvant inoculation (day 7).  The bone surface is characterized by numerous spindle-shaped small cells (diameter = 2–3 μm; double  arrowheads), cell processes  of these cells (arrowheads),  and long cell processes extending from the osteocytes  (arrow). (c) N-syndecan is  detected for the first time at  day 10 (arrows). N-syndecan  is expressed on the spindle-shaped small cells (arrow, diameter of the cells = 2–3  μm) and on their long slender cell processes (double arrowheads). (d) N-syndecan  is expressed (arrow) by the  osteoblast-like cells (ob-l)  characterized by cuboid-shaped large cell soma (diameter = 8–12 μm), rich  rough ER (+), and Golgi apparatus (asterisk) at day 14.  (e) N-syndecan expression  remaining on the cell surface  of osteocyte-like cells (oc-l)  characterized by lens-shaped  small cell soma at day 21 (diameter of the cells = 3–4  μm). These cells have not yet developed gap junctions with the neighboring cells (asterisk), a typical feature of fully differentiated osteocytes. (f) N-syndecan is not expressed by the fully differentiated osteocytes characterized by satellite-shaped cell soma with the cell processes radiating into the mineralized bone matrix at day 28 (arrows). The rectangles in c–e indicate the insets. Bars: (a) 4 μm; (b) 2.3 μm;  (c) 2 μm; (d) 1.9 μm; (e) 2.6 μm; (f) 3.2 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2132954&req=5

Figure 6: Electron-microscopic characterization of N-syndecan–expressing cells. (a) N-syndecan is not expressed by any cell types of the healthy adult bone (oc, osteocyte; ob, osteoblasts; fb, fibroblast-like cell). (b) N-syndecan is not expressed by the cellular components along the bone surface of 7 d after adjuvant inoculation (day 7). The bone surface is characterized by numerous spindle-shaped small cells (diameter = 2–3 μm; double arrowheads), cell processes of these cells (arrowheads), and long cell processes extending from the osteocytes (arrow). (c) N-syndecan is detected for the first time at day 10 (arrows). N-syndecan is expressed on the spindle-shaped small cells (arrow, diameter of the cells = 2–3 μm) and on their long slender cell processes (double arrowheads). (d) N-syndecan is expressed (arrow) by the osteoblast-like cells (ob-l) characterized by cuboid-shaped large cell soma (diameter = 8–12 μm), rich rough ER (+), and Golgi apparatus (asterisk) at day 14. (e) N-syndecan expression remaining on the cell surface of osteocyte-like cells (oc-l) characterized by lens-shaped small cell soma at day 21 (diameter of the cells = 3–4 μm). These cells have not yet developed gap junctions with the neighboring cells (asterisk), a typical feature of fully differentiated osteocytes. (f) N-syndecan is not expressed by the fully differentiated osteocytes characterized by satellite-shaped cell soma with the cell processes radiating into the mineralized bone matrix at day 28 (arrows). The rectangles in c–e indicate the insets. Bars: (a) 4 μm; (b) 2.3 μm; (c) 2 μm; (d) 1.9 μm; (e) 2.6 μm; (f) 3.2 μm.
Mentions: To identify the cell types that express N-syndecan during the adult periosteal ossification, a detailed electron-microscopical study was performed. Fully differentiated osteoblasts covering the surface of healthy adult bone (Fig. 5 c, rectangle) did not express N-syndecan (Fig. 6 a). Interestingly, the osteoblasts were not found on the surface of the damaged bone 7 d after adjuvant inoculation (day 7; Fig. 5 f, rectangle). Instead, numerous spindle-shaped cells and their cell processes, which may represent fibroblastic osteoprogenitor, were noted along the bone surface. However, these cells were not immunoreactive to N-syndecan (Fig. 6 b).

Bottom Line: We show here that heparin-binding growth-associated molecule (HB-GAM), an extracellular matrix-associated protein that enhances migratory responses in neurons, is prominently expressed in the cell matrices that act as target substrates for bone formation.The HB-GAM transgenic mice develop a phenotype characterized by an increased bone thickness.HB-GAM may thus play an important role in bone formation, probably by mediating recruitment and attachment of osteoblasts/osteoblast precursors to the appropriate substrates for deposition of new bone.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Shiga University of Medical Science, Shiga-ken, 520-2192, Japan. simai@belle.shiga-med.ac.jp

ABSTRACT
Bone has an enormous capacity for growth, regeneration, and remodeling. This capacity is largely due to induction of osteoblasts that are recruited to the site of bone formation. The recruitment of osteoblasts has not been fully elucidated, though the immediate environment of the cells is likely to play a role via cell- matrix interactions. We show here that heparin-binding growth-associated molecule (HB-GAM), an extracellular matrix-associated protein that enhances migratory responses in neurons, is prominently expressed in the cell matrices that act as target substrates for bone formation. Intriguingly, N-syndecan, which acts as a receptor for HB-GAM, is expressed by osteoblasts/osteoblast precursors, whose ultrastructural phenotypes suggest active cell motility. The hypothesis that HB-GAM/N-syndecan interaction mediates osteoblast recruitment, as inferred from developmental studies, was tested using osteoblast-type cells that express N-syndecan abundantly. These cells migrate rapidly to HB-GAM in a haptotactic transfilter assay and in a migration assay where HB-GAM patterns were created on culture wells. The mechanism of migration is similar to that previously described for the HB-GAM-induced migratory response of neurons. Our hypothesis that HB-GAM/N-syndecan interaction participates in regulation of osteoblast recruitment was tested using two different in vivo models: an adjuvant-induced arthritic model and a transgenic model. In the adjuvant-induced injury model, the expression of HB-GAM and of N-syndecan is strongly upregulated in the periosteum accompanying the regenerative response of bone. In the transgenic model, the HB-GAM expression is maintained in mesenchymal tissues with the highest expression in the periosteum. The HB-GAM transgenic mice develop a phenotype characterized by an increased bone thickness. HB-GAM may thus play an important role in bone formation, probably by mediating recruitment and attachment of osteoblasts/osteoblast precursors to the appropriate substrates for deposition of new bone.

Show MeSH
Related in: MedlinePlus