Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Abstract

Osteoarthritis (OA) induces inflammation and degeneration of all joint components including cartilage, joint capsule, bone and bone marrow, and ligaments. Particularly intraarticular ligaments, which connect the articulating bones such as the anterior cruciate ligament (ACL) and meniscotibial ligaments, fixing the fibrocartilaginous menisci to the tibial bone, are prone to the inflamed joint milieu in OA. However, the pathogenesis of ligament degeneration on the cellular level, most likely triggered by OA associated inflammation, remains poorly understood. Hence, this review sheds light into the intimate interrelation between ligament degeneration, synovitis, joint cartilage degradation, and dysbalanced subchondral bone remodeling. Various features of ligament degeneration accompanying joint cartilage degradation have been reported including chondroid metaplasia, cyst formation, heterotopic ossification, and mucoid and fatty degenerations. The entheses of ligaments, fixing ligaments to the subchondral bone, possibly influence the localization of subchondral bone lesions. The transforming growth factor (TGF)β/bone morphogenetic (BMP) pathway could present a link between degeneration of the osteochondral unit and ligaments with misrouted stem cell differentiation as one likely reason for ligament degeneration, but less studied pathways such as complement activation could also contribute to inflammation. Facilitation of OA progression by changed biomechanics of degenerated ligaments should be addressed in more detail in the future.

Enhanced Growth of Lapine Anterior Cruciate Ligament-Derived Fibroblasts on Scaffolds Embroidered from Poly(l-lactide-co-ε-caprolactone) and Polylactic Acid Threads Functionalized by Fluorination and Hexamethylene Diisocyanate Cross-Linked Collagen Foams

“…The parallel cell arrangement and longitudinal orientation according to the thread direction observed in the present study by SEM and live/dead staining is comparable to cell alignment in the native ACL [47] and was observed in another scaffold type consisting of braided nanofibers [48].…”

“…Cells were detached with 0.05% typsin/0.02% EDTA (Merck KGaA, Darmstadt, Germany) and counted with a hemocytometer. Spheroids were achieved by using the hanging drop method as described previously [47] with a cell number of 2.5 × 10 4 per spheroid. After two days of spheroid formation at 37 • C and 5% CO 2 , they were carefully harvested.…”

Exosomes: roles and therapeutic potential in osteoarthritis

“…A previous study revealed that the degeneration of the intraarticular ligament was highly associated with cartilage and bone damage during the OA process. 151 Destruction of ligament integrity, such as the cruciate ligament, seriously decreased joint stability and promoted the development of knee OA, indicating an important role of the ligament in OA disease. [152][153][154] Zhao et al isolated exosomes from periodontal ligament stem cells using an ultracentrifugation method and identified their exosomal characteristics by TEM, western blot and nanosight tracing analysis.…”

Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

“…During the development of OA, degeneration of all joint constituents including cartilage, synovial membrane, bone, bone marrow and ligaments occurs [36,43]. The biological imbalance and the mechanical stress lead to a pathological situation with altered chondrocyte behavior releasing inflammatory mediators and ECM destruction enzymes [35,[44][45][46].…”