Abstract
A large proportion of ankle osteoarthritis (OA) has an early onset and is post‐traumatic. Surgical interventions have low patient satisfaction and relatively poor clinical outcome, whereas joint‐preserving treatments, which rely on endogenous multipotential stromal cells (MSCs), result in suboptimal repair. This study investigates MSC presence and potency in OA‐affected talocrural osteochondral tissue. Bone volume fraction (BV/TV) changes for the loading region trabecular volume and subchondral bone plate (SBP) thickness in OA compared with healthy tissue were investigated using microcomputed tomography. CD271‐positive MSC topography was related to bone and cartilage damage in OA tissue, and in vitro MSC potency was compared with control healthy iliac crest (IC) MSCs. A 1.3‐ to 2.5‐fold SBP thickening was found in both OA talus and tibia, whereas BV/TV changes were depth‐dependent. MSCs were abundant in OA talus and tibia, with similar colony characteristics. Tibial and talar MSCs were tripotential, but talar MSCs had 10‐fold lower adipogenesis and twofold higher chondrogenesis than IC MSCs (P = .01 for both). Cartilage damage in both OA tibia and talus correlated with SBP thickening and CD271+ MSCs was 1.4‐ to twofold more concentrated near the SBP. This work shows multipotential MSCs are present in OA talocrural subchondral bone, with their topography suggesting ongoing involvement in SBP thickening. Potentially, biomechanical stimulation could augment the chondrogenic differentiation of MSCs for joint‐preserving treatments.
Highlights
Osteoarthritis (OA) has an estimated prevalence of 10%-30% worldwide[1,2]; most interventions treat the symptoms of the disease, rather than the cause
There was a clear association between the grade of cartilage damage and the amount of CD271 staining within trabecular spaces, with significant differences in the tibia between grade 3 and 6 (P = .008), and 4 and 6 (P = .0197) (Figure 5D)
We show for the first-time subchondral bone multipotential stromal cells (MSCs) presence in both OA talus and tibia, with both talar and tibial MSCs showing enhanced chondrogenesis and osteogenesis than control iliac crest (IC) MSCs, and reduced adipogenesis in talar MSCs
Summary
Osteoarthritis (OA) has an estimated prevalence of 10%-30% worldwide[1,2]; most interventions treat the symptoms of the disease, rather than the cause. We show that MSCs with an osteochondral-reparative phenotype are present in ankle OA joint and, notably localize near the OA joint surface, are highly correlated with regions of bone sclerosis, as such may be key drivers. These findings will help to inform future developments of enhanced regenerative therapies, such as microfracture, to enable an optimal release of MSC from the talar bone
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