Limits...
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.

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

α-SMA and STRO-1 expression. (A-D) α-SMA; (E-H) STRO-1. (A,E) ACL from young normal knee; (B,F) ACL from aging knee; (C,G) fibroblast-like cell aggregates in the degenerated ACL; (D,H) chondrocyte-like cell aggregates in the degenerated ACL. Black arrows, positive cells; white arrows, negative cells. (Original magnification ×40). (I) The graph represents the percentage (mean ± SEM) of α-SMA- and STRO-1-positive cells. **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3672799&req=5

Figure 3: α-SMA and STRO-1 expression. (A-D) α-SMA; (E-H) STRO-1. (A,E) ACL from young normal knee; (B,F) ACL from aging knee; (C,G) fibroblast-like cell aggregates in the degenerated ACL; (D,H) chondrocyte-like cell aggregates in the degenerated ACL. Black arrows, positive cells; white arrows, negative cells. (Original magnification ×40). (I) The graph represents the percentage (mean ± SEM) of α-SMA- and STRO-1-positive cells. **P < 0.01.

Mentions: α-Smooth muscle actin (α-SMA) is a marker of myofibroblasts and also immature or stem cells [21]. α-SMA-positive cells were observed in dense collagenous tissue, perivascular area, and lining cells in the synovial sheath. In normal ACLs, 43.1% of ligament cells were positive (Figure 3A). The number of positive cells decreased with aging (10.3% ± 3.4%; P < 0.0001) (Figure 3B). But the average percentage of α-SMA positive cells in degenerated ACLs (55.9 ± 3.6%) was higher than that in the aging group (10.3% ± 3.4%; P < 0.0001). 72.4% of chondrocyte-like cells and 39.4% of fibroblast-like cell aggregates were α-SMA positive (Figure 3C, 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)

α-SMA and STRO-1 expression. (A-D) α-SMA; (E-H) STRO-1. (A,E) ACL from young normal knee; (B,F) ACL from aging knee; (C,G) fibroblast-like cell aggregates in the degenerated ACL; (D,H) chondrocyte-like cell aggregates in the degenerated ACL. Black arrows, positive cells; white arrows, negative cells. (Original magnification ×40). (I) The graph represents the percentage (mean ± SEM) of α-SMA- and STRO-1-positive cells. **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: α-SMA and STRO-1 expression. (A-D) α-SMA; (E-H) STRO-1. (A,E) ACL from young normal knee; (B,F) ACL from aging knee; (C,G) fibroblast-like cell aggregates in the degenerated ACL; (D,H) chondrocyte-like cell aggregates in the degenerated ACL. Black arrows, positive cells; white arrows, negative cells. (Original magnification ×40). (I) The graph represents the percentage (mean ± SEM) of α-SMA- and STRO-1-positive cells. **P < 0.01.
Mentions: α-Smooth muscle actin (α-SMA) is a marker of myofibroblasts and also immature or stem cells [21]. α-SMA-positive cells were observed in dense collagenous tissue, perivascular area, and lining cells in the synovial sheath. In normal ACLs, 43.1% of ligament cells were positive (Figure 3A). The number of positive cells decreased with aging (10.3% ± 3.4%; P < 0.0001) (Figure 3B). But the average percentage of α-SMA positive cells in degenerated ACLs (55.9 ± 3.6%) was higher than that in the aging group (10.3% ± 3.4%; P < 0.0001). 72.4% of chondrocyte-like cells and 39.4% of fibroblast-like cell aggregates were α-SMA positive (Figure 3C, 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