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Acute Osteoclast Activity following Subchondral Drilling Is Promoted by Chitosan and Associated with Improved Cartilage Repair Tissue Integration.

Chen G, Sun J, Lascau-Coman V, Chevrier A, Marchand C, Hoemann CD - Cartilage (2011)

Bottom Line: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks.Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks.Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.

ABSTRACT

Objective: Cartilage-bone integration is an important functional end point of cartilage repair therapy, but little is known about how to promote integration. We tested the hypothesis that chitosan-stabilized blood clot implant elicits osteoclasts to drilled cartilage defects and promotes repair and cartilage-bone integration.

Design: Bilateral trochlear defects in 15 skeletally mature rabbit knees were microdrilled and then treated with chitosan-glycerol phosphate (GP)/blood implant with fluorescent chitosan tracer and thrombin to accelerate in situ solidification or with thrombin alone. Chitosan clearance, osteoclast density, and osteochondral repair were evaluated at 1, 2, and 8 weeks at the outside, edge, and through the proximal microdrill holes.

Results: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks. Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks. Implants elicited 2-fold more osteoclasts relative to controls (P < 0.001), a more complete drill hole bone repair, and improved cartilage-bone integration and histological tissue quality. Treated and control 8-week cartilage repair tissues contained 85% collagen type II. After 8 weeks of repair, subchondral osteoclast density correlated positively with bone-cartilage repair tissue integration (P < 0.0005).

Conclusions: Chitosan-GP/blood implant amplified the acute influx of subchondral osteoclasts through indirect mechanisms, leading to significantly improved repair and cartilage-bone integration without inducing net bone resorption. Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.

No MeSH data available.


Related in: MedlinePlus

Osteoclast morphology in nondecalcified plastic sections from repairing defects. (A) An example of multinucleated osteoclast (white arrow) adhering to bone lining the drill hole adjacent to viable osteocytes (white arrowheads, Goldner-stained section from 1-week repair, treated defect). (B) An osteoclast (white arrow) and a typical mononuclear TRAP+ cell detected in granulation tissue with nonosteoclast morphology (open arrowhead, TRAP-stained section with methyl green counterstain from 2-week repair).
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fig4-1947603510381096: Osteoclast morphology in nondecalcified plastic sections from repairing defects. (A) An example of multinucleated osteoclast (white arrow) adhering to bone lining the drill hole adjacent to viable osteocytes (white arrowheads, Goldner-stained section from 1-week repair, treated defect). (B) An osteoclast (white arrow) and a typical mononuclear TRAP+ cell detected in granulation tissue with nonosteoclast morphology (open arrowhead, TRAP-stained section with methyl green counterstain from 2-week repair).

Mentions: Osteoclasts accumulated below drilled cartilage defects in 3 distinct phases: resorption, remodeling, and endochondral cartilage repair formation. At 1 week postoperatively, osteoclasts accumulated along the edges of the drill holes (Fig. 3 A-B), and in some treated defects, osteoclasts appeared to be tunneling toward the chondral defect surface (Fig. 3C). After 2 weeks, osteoclasts appeared in remodeling new woven bone at the base of the repairing drill holes, with osteoblasts in the vicinity (Fig. 3 D-F). At 8 weeks, osteoclasts were detected in vascularized bone pores in the subchondral bone plate below integrated endochondral repair tissue (Fig. 3 G-J). Except for the top of the drill holes, osteoclasts below treated defects at 1 to 2 weeks did not appear to be in direct contact with RITC-chitosan particles (compare Fig. 2C with Fig. 3E). Higher osteoclast density below treated defects at 8 weeks was not directly due to the chitosan implant, which was completely cleared at this time point (Fig. 1F). Although apoptotic osteocytes can mediate osteoclast formation in some contexts,19 at 1 week after drilling, we found no clear evidence of osteocyte apoptosis at the drill hole edges lined with osteoclasts (Fig. 4A). Small mononuclear TRAP+ cells with spindle-shaped (nonosteoclast) morphology were detected in some drill hole granulation tissues in both control and treated defects (Fig. 4B, open arrow); these cells were excluded from osteoclast density measurements.


Acute Osteoclast Activity following Subchondral Drilling Is Promoted by Chitosan and Associated with Improved Cartilage Repair Tissue Integration.

Chen G, Sun J, Lascau-Coman V, Chevrier A, Marchand C, Hoemann CD - Cartilage (2011)

Osteoclast morphology in nondecalcified plastic sections from repairing defects. (A) An example of multinucleated osteoclast (white arrow) adhering to bone lining the drill hole adjacent to viable osteocytes (white arrowheads, Goldner-stained section from 1-week repair, treated defect). (B) An osteoclast (white arrow) and a typical mononuclear TRAP+ cell detected in granulation tissue with nonosteoclast morphology (open arrowhead, TRAP-stained section with methyl green counterstain from 2-week repair).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4300782&req=5

fig4-1947603510381096: Osteoclast morphology in nondecalcified plastic sections from repairing defects. (A) An example of multinucleated osteoclast (white arrow) adhering to bone lining the drill hole adjacent to viable osteocytes (white arrowheads, Goldner-stained section from 1-week repair, treated defect). (B) An osteoclast (white arrow) and a typical mononuclear TRAP+ cell detected in granulation tissue with nonosteoclast morphology (open arrowhead, TRAP-stained section with methyl green counterstain from 2-week repair).
Mentions: Osteoclasts accumulated below drilled cartilage defects in 3 distinct phases: resorption, remodeling, and endochondral cartilage repair formation. At 1 week postoperatively, osteoclasts accumulated along the edges of the drill holes (Fig. 3 A-B), and in some treated defects, osteoclasts appeared to be tunneling toward the chondral defect surface (Fig. 3C). After 2 weeks, osteoclasts appeared in remodeling new woven bone at the base of the repairing drill holes, with osteoblasts in the vicinity (Fig. 3 D-F). At 8 weeks, osteoclasts were detected in vascularized bone pores in the subchondral bone plate below integrated endochondral repair tissue (Fig. 3 G-J). Except for the top of the drill holes, osteoclasts below treated defects at 1 to 2 weeks did not appear to be in direct contact with RITC-chitosan particles (compare Fig. 2C with Fig. 3E). Higher osteoclast density below treated defects at 8 weeks was not directly due to the chitosan implant, which was completely cleared at this time point (Fig. 1F). Although apoptotic osteocytes can mediate osteoclast formation in some contexts,19 at 1 week after drilling, we found no clear evidence of osteocyte apoptosis at the drill hole edges lined with osteoclasts (Fig. 4A). Small mononuclear TRAP+ cells with spindle-shaped (nonosteoclast) morphology were detected in some drill hole granulation tissues in both control and treated defects (Fig. 4B, open arrow); these cells were excluded from osteoclast density measurements.

Bottom Line: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks.Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks.Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.

ABSTRACT

Objective: Cartilage-bone integration is an important functional end point of cartilage repair therapy, but little is known about how to promote integration. We tested the hypothesis that chitosan-stabilized blood clot implant elicits osteoclasts to drilled cartilage defects and promotes repair and cartilage-bone integration.

Design: Bilateral trochlear defects in 15 skeletally mature rabbit knees were microdrilled and then treated with chitosan-glycerol phosphate (GP)/blood implant with fluorescent chitosan tracer and thrombin to accelerate in situ solidification or with thrombin alone. Chitosan clearance, osteoclast density, and osteochondral repair were evaluated at 1, 2, and 8 weeks at the outside, edge, and through the proximal microdrill holes.

Results: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks. Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks. Implants elicited 2-fold more osteoclasts relative to controls (P < 0.001), a more complete drill hole bone repair, and improved cartilage-bone integration and histological tissue quality. Treated and control 8-week cartilage repair tissues contained 85% collagen type II. After 8 weeks of repair, subchondral osteoclast density correlated positively with bone-cartilage repair tissue integration (P < 0.0005).

Conclusions: Chitosan-GP/blood implant amplified the acute influx of subchondral osteoclasts through indirect mechanisms, leading to significantly improved repair and cartilage-bone integration without inducing net bone resorption. Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.

No MeSH data available.


Related in: MedlinePlus