Osteophytes and fracture calluses share developmental milestones and are diminished by unloading

Abstract

Osteophytes are a typical radiographic finding during osteoarthritis (OA), but the mechanisms leading to their formation are not well known. Comparatively, fracture calluses have been studied extensively; therefore, drawing comparisons between osteophytes and fracture calluses may lead to a deeper understanding of osteophyte formation. In this study, we compared the time courses of osteophyte and fracture callus formation, and investigated mechanisms contributing to development of these structure. Additionally, we investigated the effect of mechanical unloading on the formation of both fracture calluses and osteophytes. Mice underwent either transverse femoral fracture or non-invasive anterior cruciate ligament rupture. Fracture callus and osteophyte size and ossification were evaluated after 3, 5, 7, 14, 21, or 28 days. Additional mice were subjected to hindlimb unloading after injury for 3, 7, or 14 days. Protease activity and gene expression profiles after injury were evaluated after 3 or 7 days of normal ambulation or hindlimb unloading using in vivo fluorescence reflectance imaging (FRI) and quantitative PCR. We found that fracture callus and osteophyte growth achieved similar developmental milestones, but fracture calluses formed and ossified at earlier time points. Hindlimb unloading ultimately led to a threefold decrease in chondro/osteophyte area, and a twofold decrease in fracture callus area. Unloading was also associated with decreased inflammation and protease activity in injured limbs detected with FRI, particularly following ACL rupture. qPCR analysis revealed disparate cellular responses in fractured femurs and injured joints, suggesting that fracture calluses and osteophytes may form via different inflammatory, anabolic, and catabolic pathways. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:699-710, 2018.

Multiscale bone quality analysis in osteoarthritic knee joints reveal a role of the mechanosensory osteocyte network in osteophytes

“…(ii) Dayal et al reported a reduced laxity in anterior posterior with osteophyte growth 19 . (iii) In a mouse model following anterior cruciate ligament transection, the initial increase in joint laxity was reduced significantly over time and this development correlated with the formation of osteophytes 20 . Yet, a clinical study to confirm improvement of OA-related pain and immobilization during early disease stages is still lacking.…”

Attenuation of Post‐Traumatic Osteoarthritis After Anterior Cruciate Ligament Injury Via Inhibition of Hedgehog Signaling

“…The sections were stained with Safranin‐O–fast‐green to assess osteophyte formation and articular cartilage degeneration. The osteophyte (including chondrophyte) areas were quantified using freehand traces in ImageJ (National Institutes of Health, Bethesda, MD) . Histologic grading of articular cartilage damage severity was performed using the scoring system reported by Kamekura et al, which consisted of a 0‐4 scale for cartilage degeneration (0: No apparent changes; 1: Loss of superficial zone in articular cartilage; 2: Defects limited above tidemark; 3: Defects extending to calcified cartilage; 4: Exposure of subchondral bone) and a 0‐3 scale for osteophyte formation (0: None; 1: Formation of cartilage‐like tissues; 2: Increase in cartilaginous matrix; 3: Endochondral ossification).…”

“…ImageJ (National Institutes of Health, Bethesda, MD). 21,22 Histologic grading of articular cartilage damage severity was performed using the scoring system reported by Kamekura et al, 7 which consisted of a 0-4 scale for cartilage degeneration (0: No apparent changes; 1: Loss of superficial zone in articular cartilage; 2: Defects limited above tidemark; 3: Defects extending to calcified cartilage; 4: Exposure of subchondral bone) and a 0-3 scale for osteophyte formation (0: None; 1: Formation of cartilage-like tissues; 2: Increase in cartilaginous matrix; 3: Endochondral ossification). Previously, there were multiple scoring systems for assessing a murine osteoarthritis model.…”

The Clinical Efficacy, Safety and Biomechanical Mechanism of Tai Chi in Patients with Knee Osteoarthritis: Study Protocol for a Randomized Controlled Trial

“…Secondly, pain, as the rst symptom and main treatment factor of KOA patients, seriously affects the physical and mental health of patients [10]. It has been found that KOA pain originates not only from peripheral nerve responses caused by joint and surrounding tissue injury or in ammatory stimulation of peripheral receptors [11,12], but also from pain sensitization of central neurons caused by increased activity of descending ber pain pathways or loss of anti-in ammatory effects in the central nervous system [13,14]. There has also been evidence in recent years that [15,16], the source of KOA pain is not limited to peripheral and central nervous system sensitization, but also affected by a range of sociocultural and psychological factors, including underlying anxiety and depression [17].…”