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Cellular and extracellular matrix changes in anterior cruciate ligaments during human knee aging and osteoarthritis.

Hasegawa A, Nakahara H, Kinoshita M, Asahara H, Koziol J, Lotz MK - Arthritis Res. Ther. (2013)

Bottom Line: Alpha-smooth muscle actin (α-SMA), a marker of myofibroblasts and the progenitor cell marker STRO-1, decreased with aging in normal ACL.ACL aging is characterized by reduced cell density and activation.In contrast, ACL degeneration is associated with cell recruitment or proliferation, including progenitor cells or myofibroblasts.

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ABSTRACT

Introduction: Anterior cruciate ligament (ACL) degeneration is observed in most osteoarthritis (OA)-affected knee joints. However, the specific spatial and temporal relations of these changes and their association with extracellular matrix (ECM) degeneration are not well understood. The objective of this study was to characterize the patterns and relations of aging-related and OA-associated changes in ACL cells and the ECM.

Methods: Human knee joints from 80 donors (age 23 through 94) were obtained at autopsy. ACL degeneration was assessed histologically by using a quantitative scoring system. Tissue sections were analyzed for cell density, cell organization, ECM components, ECM-degrading enzymes and markers of differentiation, proliferation, and stem cells.

Results: Total cell number in normal ACL decreased with aging but increased in degenerated ACL, because of the formation of perivascular cell aggregates and islands of chondrocyte-like cells. Matrix metalloproteinase (MMP)-1, -3, and -13 expression was reduced in aging ACL but increased in degenerated ACL, mainly in the chondrocyte-like cells. Collagen I was expressed throughout normal and degenerated ACL. Collagen II and X were detected only in the areas with chondroid metaplasia, which also expressed collagen III. Sox9, Runt-related transcription factor 2 (Runx2), and scleraxis expression was increased in the chondrocyte-like cells in degenerated ACL. Alpha-smooth muscle actin (α-SMA), a marker of myofibroblasts and the progenitor cell marker STRO-1, decreased with aging in normal ACL. In degenerated ACL, the new cell aggregates were positive for α-SMA and STRO-1.

Conclusions: ACL aging is characterized by reduced cell density and activation. In contrast, ACL degeneration is associated with cell recruitment or proliferation, including progenitor cells or myofibroblasts. Abnormally differentiated chondrocyte-like cell aggregates in degenerated ACL produce abnormal ECM and may predispose to mechanical failure.

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Collagen types I, II, and III. (A-D) Collagen type I, (E-H) collagen type II, (I-L) collagen type III (A, E, I) ACL from young normal knee; (B, F, J) ACL from aging knee; (C, G, K) fibroblast-like cell aggregates in the degenerated ACL; (D, H, L) chondrocyte-like cell aggregates in the degenerated ACL. Most collagen bundles were type I collagen positive (A-D), however, staining intensity of the ECM around chondrocyte-like cell aggregates was lower (black arrows). Type II collagen-positive area is observed around chondrocyte-like cell aggregates (white arrows). In the normal ACL, type III collagen is located within the loose connective tissue (black arrowheads) that divides the collagen fibrils of the ligament into small bundles but not dense collagenous tissues. In the degenerated ACL, type III collagen (white arrowheads). (Original magnification ×40).
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Figure 5: Collagen types I, II, and III. (A-D) Collagen type I, (E-H) collagen type II, (I-L) collagen type III (A, E, I) ACL from young normal knee; (B, F, J) ACL from aging knee; (C, G, K) fibroblast-like cell aggregates in the degenerated ACL; (D, H, L) chondrocyte-like cell aggregates in the degenerated ACL. Most collagen bundles were type I collagen positive (A-D), however, staining intensity of the ECM around chondrocyte-like cell aggregates was lower (black arrows). Type II collagen-positive area is observed around chondrocyte-like cell aggregates (white arrows). In the normal ACL, type III collagen is located within the loose connective tissue (black arrowheads) that divides the collagen fibrils of the ligament into small bundles but not dense collagenous tissues. In the degenerated ACL, type III collagen (white arrowheads). (Original magnification ×40).

Mentions: To assess ECM changes, we performed immunohistochemistry for collagens type I, II, III, and X and aggrecan. In the normal and aging ACL, most collagen bundles were type I collagen positive (Figure 5A, B). In the degenerated ACL, ECM around fibroblast-like cell aggregates were type I collagen positive; however, staining intensity of ECM around chondrocyte-like cell aggregates was lower (Figure 5C, D).


Cellular and extracellular matrix changes in anterior cruciate ligaments during human knee aging and osteoarthritis.

Hasegawa A, Nakahara H, Kinoshita M, Asahara H, Koziol J, Lotz MK - Arthritis Res. Ther. (2013)

Collagen types I, II, and III. (A-D) Collagen type I, (E-H) collagen type II, (I-L) collagen type III (A, E, I) ACL from young normal knee; (B, F, J) ACL from aging knee; (C, G, K) fibroblast-like cell aggregates in the degenerated ACL; (D, H, L) chondrocyte-like cell aggregates in the degenerated ACL. Most collagen bundles were type I collagen positive (A-D), however, staining intensity of the ECM around chondrocyte-like cell aggregates was lower (black arrows). Type II collagen-positive area is observed around chondrocyte-like cell aggregates (white arrows). In the normal ACL, type III collagen is located within the loose connective tissue (black arrowheads) that divides the collagen fibrils of the ligament into small bundles but not dense collagenous tissues. In the degenerated ACL, type III collagen (white arrowheads). (Original magnification ×40).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672799&req=5

Figure 5: Collagen types I, II, and III. (A-D) Collagen type I, (E-H) collagen type II, (I-L) collagen type III (A, E, I) ACL from young normal knee; (B, F, J) ACL from aging knee; (C, G, K) fibroblast-like cell aggregates in the degenerated ACL; (D, H, L) chondrocyte-like cell aggregates in the degenerated ACL. Most collagen bundles were type I collagen positive (A-D), however, staining intensity of the ECM around chondrocyte-like cell aggregates was lower (black arrows). Type II collagen-positive area is observed around chondrocyte-like cell aggregates (white arrows). In the normal ACL, type III collagen is located within the loose connective tissue (black arrowheads) that divides the collagen fibrils of the ligament into small bundles but not dense collagenous tissues. In the degenerated ACL, type III collagen (white arrowheads). (Original magnification ×40).
Mentions: To assess ECM changes, we performed immunohistochemistry for collagens type I, II, III, and X and aggrecan. In the normal and aging ACL, most collagen bundles were type I collagen positive (Figure 5A, B). In the degenerated ACL, ECM around fibroblast-like cell aggregates were type I collagen positive; however, staining intensity of ECM around chondrocyte-like cell aggregates was lower (Figure 5C, D).

Bottom Line: Alpha-smooth muscle actin (α-SMA), a marker of myofibroblasts and the progenitor cell marker STRO-1, decreased with aging in normal ACL.ACL aging is characterized by reduced cell density and activation.In contrast, ACL degeneration is associated with cell recruitment or proliferation, including progenitor cells or myofibroblasts.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Anterior cruciate ligament (ACL) degeneration is observed in most osteoarthritis (OA)-affected knee joints. However, the specific spatial and temporal relations of these changes and their association with extracellular matrix (ECM) degeneration are not well understood. The objective of this study was to characterize the patterns and relations of aging-related and OA-associated changes in ACL cells and the ECM.

Methods: Human knee joints from 80 donors (age 23 through 94) were obtained at autopsy. ACL degeneration was assessed histologically by using a quantitative scoring system. Tissue sections were analyzed for cell density, cell organization, ECM components, ECM-degrading enzymes and markers of differentiation, proliferation, and stem cells.

Results: Total cell number in normal ACL decreased with aging but increased in degenerated ACL, because of the formation of perivascular cell aggregates and islands of chondrocyte-like cells. Matrix metalloproteinase (MMP)-1, -3, and -13 expression was reduced in aging ACL but increased in degenerated ACL, mainly in the chondrocyte-like cells. Collagen I was expressed throughout normal and degenerated ACL. Collagen II and X were detected only in the areas with chondroid metaplasia, which also expressed collagen III. Sox9, Runt-related transcription factor 2 (Runx2), and scleraxis expression was increased in the chondrocyte-like cells in degenerated ACL. Alpha-smooth muscle actin (α-SMA), a marker of myofibroblasts and the progenitor cell marker STRO-1, decreased with aging in normal ACL. In degenerated ACL, the new cell aggregates were positive for α-SMA and STRO-1.

Conclusions: ACL aging is characterized by reduced cell density and activation. In contrast, ACL degeneration is associated with cell recruitment or proliferation, including progenitor cells or myofibroblasts. Abnormally differentiated chondrocyte-like cell aggregates in degenerated ACL produce abnormal ECM and may predispose to mechanical failure.

Show MeSH
Related in: MedlinePlus