Abstract
IntroductionAnterior 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.MethodsHuman 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.ResultsTotal 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.ConclusionsACL 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.
Highlights
Anterior cruciate ligament (ACL) degeneration is observed in most osteoarthritis (OA)-affected knee joints
Cell density and cell arrangements The cell density in histologically normal ACLs from young donors (60 years old), with minimal changes in the articular cartilage (Grade I cartilage) (P = 0.023) (Figure 1A, B, I)
Fibroblast-like cell aggregates were present in 12 (44.4%) of 27 degenerated ACL groups, and this was significantly more common than normal (0 of 8; none) and aging group (5 (13.5%) of 37) (P = 0.004 with c2 analysis)
Summary
Anterior cruciate ligament (ACL) degeneration is observed in most osteoarthritis (OA)-affected knee joints. 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. Anterior cruciate ligament (ACL) degeneration is observed in most osteoarthritis (OA)-affected knee joints [1,2]. Our recent observations indicate that histologic changes in ACL, in particular chondroid metaplasia, collagen fiber disorganization, and mucoid degeneration, can occur before the onset of significant cartilage degeneration in individuals without a history of knee trauma and at a relatively young age [1]. It is possible that changes in ACL cells and extracellular. Chondroid metaplasia is a feature of degenerated ACL [2,5,6,7] and may precede and predispose to structural failure [3,8]
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