Abstract
Osteoarthritis (OA) is a common age-related disease with complex pathophysiology. It is characterized by wide-ranging tissue damage and ultimate biomechanical failure of the whole joint. However, signs of tissue adaptation and attempted repair responses are evident in OA-affected osteochondral tissues. Highlighted in this review article is the role of bone-resident mesenchymal stem cells (MSCs) in these bone remodeling responses, and a proposal that targeting MSC activities in OA subchondral bone could represent a novel approach for intrinsic joint regeneration in OA. The development of these therapies will require better understanding of MSC proliferation, migration and differentiation patterns in relation to OA tissue damage and further clarification of the molecular signaling events in these MSCs during disease progression.
Highlights
Therapies aimed to restore mesenchymal stem cells (MSCs) bone remodeling & other activities in OA As mentioned above, subchondral bone abnormalities observed in OA, such as subchondral plate thickening, osteophyte formation and BM lesions (BMLs), which are characterized by thicker but less mineralized softer bone, suggest that the OA process is associated with altered bone remodeling activity around the site of damage
In the sections below we describe how our current understanding of the state of MSCs and their descendants in OA subchondral bone could lead to novel approaches for OA treatment
Having identified potential MSC modifiers such as TGF-β and SDF-1α, steps would require development of optimal routes and procedures for their administration that would be as a consequence of a better appreciation of OA as a disease of the whole joint
Summary
A more recent OA animal study, in which anterior cruciate ligament transection was used to induce OA and nestin was employed as a marker for identifying and tracking MSCs, has shown their accumulation and deranged differentiation in OA affected future science group joints and suggested to be a result of the altered TGF-β availability in these areas [40]. Therapies aimed to restore MSC bone remodeling & other activities in OA As mentioned above, subchondral bone abnormalities observed in OA, such as subchondral plate thickening, osteophyte formation and BMLs, which are characterized by thicker but less mineralized softer bone, suggest that the OA process is associated with altered bone remodeling activity around the site of damage.
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