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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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Cell organization, cell density, and Ki-67 expression in ACL. (A-D) H&E staining; (E-H) Ki-67 (original magnification ×40). Sections of ACL representing (A, E) normal cell distribution in ACL from young normal knee; (B, F) hypocellular ACL from aging knee; (C, G) fibroblast-like cell aggregates in degenerated ACL; (D, H) chondrocyte-like cell aggregates in degenerated ACL. Black arrows, Ki-67-positive cells; white arrows, Ki-67-negative cells. The graph (I) represents the total cell density in each ACL group. The graph (J) represents the percentage of Ki-67-positive cells. The results are presented as mean ± SEM. *P < 0.05; **P < 0.01.
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Figure 1: Cell organization, cell density, and Ki-67 expression in ACL. (A-D) H&E staining; (E-H) Ki-67 (original magnification ×40). Sections of ACL representing (A, E) normal cell distribution in ACL from young normal knee; (B, F) hypocellular ACL from aging knee; (C, G) fibroblast-like cell aggregates in degenerated ACL; (D, H) chondrocyte-like cell aggregates in degenerated ACL. Black arrows, Ki-67-positive cells; white arrows, Ki-67-negative cells. The graph (I) represents the total cell density in each ACL group. The graph (J) represents the percentage of Ki-67-positive cells. The results are presented as mean ± SEM. *P < 0.05; **P < 0.01.

Mentions: The cell density in histologically normal ACLs from young donors (<45 years old) with normal (Grade 0) knee cartilage was 301.4 ± 36.6/mm2, and this was significantly reduced to 188.9 ± 13.0/mm2 in ACL from old donors (>60 years old), with minimal changes in the articular cartilage (Grade I cartilage) (P = 0.023) (Figure 1A, B, I). In contrast, cell density in degenerated ACLs from old donors (>60 years old) with degenerated cartilage (Grade II to IV) (358.3 ± 51.8/mm2) was as high as that in the ACL from young donors (Figure 1A, C, 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)

Cell organization, cell density, and Ki-67 expression in ACL. (A-D) H&E staining; (E-H) Ki-67 (original magnification ×40). Sections of ACL representing (A, E) normal cell distribution in ACL from young normal knee; (B, F) hypocellular ACL from aging knee; (C, G) fibroblast-like cell aggregates in degenerated ACL; (D, H) chondrocyte-like cell aggregates in degenerated ACL. Black arrows, Ki-67-positive cells; white arrows, Ki-67-negative cells. The graph (I) represents the total cell density in each ACL group. The graph (J) represents the percentage of Ki-67-positive cells. The results are presented as mean ± SEM. *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Cell organization, cell density, and Ki-67 expression in ACL. (A-D) H&E staining; (E-H) Ki-67 (original magnification ×40). Sections of ACL representing (A, E) normal cell distribution in ACL from young normal knee; (B, F) hypocellular ACL from aging knee; (C, G) fibroblast-like cell aggregates in degenerated ACL; (D, H) chondrocyte-like cell aggregates in degenerated ACL. Black arrows, Ki-67-positive cells; white arrows, Ki-67-negative cells. The graph (I) represents the total cell density in each ACL group. The graph (J) represents the percentage of Ki-67-positive cells. The results are presented as mean ± SEM. *P < 0.05; **P < 0.01.
Mentions: The cell density in histologically normal ACLs from young donors (<45 years old) with normal (Grade 0) knee cartilage was 301.4 ± 36.6/mm2, and this was significantly reduced to 188.9 ± 13.0/mm2 in ACL from old donors (>60 years old), with minimal changes in the articular cartilage (Grade I cartilage) (P = 0.023) (Figure 1A, B, I). In contrast, cell density in degenerated ACLs from old donors (>60 years old) with degenerated cartilage (Grade II to IV) (358.3 ± 51.8/mm2) was as high as that in the ACL from young donors (Figure 1A, C, 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