Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice

Abstract

Objective Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). Design Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26μg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. Results FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. In contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. Conclusions Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression.

Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis

“…Previous studies have reported a higher average Tb.N and Tb.Th, which contributed to sclerotic changes in subchondral bone of advanced OA . In fact, the hypothesis that changes in subchondral bone might affect OA development is commonly acknowledged . Radin and Rose had originally proposed that densification of subchondral bone might lead to increased stiffness, thereby introducing adverse stress concentrations and sequential damage to articular cartilage.…”

“…(5)(6)(7) In fact, the hypothesis that changes in subchondral bone might affect OA development is commonly acknowledged. (4,9,(33)(34)(35)(36) Radin and Rose (37) had originally proposed that densification of subchondral bone might lead to increased stiffness, thereby introducing adverse stress concentrations and sequential damage to articular cartilage. Clinically, OP is another recognized factor that causes subchondral bone alterations in the functional unit of cartilage and subchondral bone.…”

Osteocyte TGFβ1‑Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis

“…It is mainly characterized by cartilage lesions, subchondral bone sclerosis and aseptic inflammation of the synovium (2). Previous studies have identified that the pathogenesis of osteoarthritis (OA) is initially caused by structural modification in the subchondral bone in response to changes in the mechanical environment (3)(4)(5). It has also been reported that subchondral bone of OA shows dysregulated bone modified by osteoblast and osteoclast activity (6), finally resulting in the formation of sclerosis (7).…”

Biological and Mechanical Predictors of Meniscus Function: Basic Science to Clinical Translation

“…Both in vivo animal and in vitro tissue explant models have demonstrated that increased joint translation, contact stress, and impact force can lead to cartilage degeneration . But, the question remains—how are the applied forces and system boundary conditions related to the loading conditions experienced by the human knee joint after partial meniscectomy?…”