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Title: Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture

Lubricin is an important boundary lubricant and chondroprotective glycoprotein in synovial fluid. Both increased and decreased synovial fluid lubricin concentrations have been reported in experimental post-traumatic osteoarthritis (PTOA) animal models and in naturally occurring joint injuries in humans and animals, with no consensus about how lubricin is altered in different species or injury types. Increased synovial fluid lubricin has been observed following intra-articular fracture in humans and horses and in human late-stage osteoarthritis; however, it is unknown how synovial lubricin is affected by knee-destabilizing injuries in large animals. Spontaneous rupture of cranial cruciate ligament (RCCL), the anterior cruciate ligament equivalent in quadrupeds, is a common injury in dogs often accompanied by OA. Here, clinical records, radiographs, and synovial fluid samples from 30 dogs that sustained RCCL and 9 clinically healthy dogs were analyzed. Synovial fluid lubricin concentrations were nearly 16-fold greater in RCCL joints as compared to control joints, while IL-2, IL-6, IL-8, and TNF-α concentrations did not differ between groups. Synovial fluid lubricin concentrations were correlated with the presence of radiographic OA and were elevated in three animals sustaining RCCL injury prior to the radiographic manifestation of OA, indicating that lubricin may be a potential biomarker for early joint more » injury.

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Publication Date:
Journal Name:
Scientific Reports
Nature Publishing Group
Sponsoring Org:
National Science Foundation
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  4. Background:

    Graft placement is a modifiable and often discussed surgical factor in anterior cruciate ligament (ACL) reconstruction (ACLR). However, the sensitivity of functional knee mechanics to variability in graft placement is not well understood.


    To (1) investigate the relationship of ACL graft tunnel location and graft angle with tibiofemoral kinematics in patients with ACLR, (2) compare experimentally measured relationships with those observed with a computational model to assess the predictive capabilities of the model, and (3) use the computational model to determine the effect of varying ACL graft tunnel placement on tibiofemoral joint mechanics during walking.

    Study Design:

    Controlled laboratory study.


    Eighteen participants who had undergone ACLR were tested. Bilateral ACL footprint location and graft angle were assessed using magnetic resonance imaging (MRI). Bilateral knee laxity was assessed at the completion of rehabilitation. Dynamic MRI was used to measure tibiofemoral kinematics and cartilage contact during active knee flexion-extension. Additionally, a total of 500 virtual ACLR models were created from a nominal computational knee model by varying ACL footprint locations, graft stiffness, and initial tension. Laxity tests, active knee extension, and walking were simulated with each virtual ACLR model. Linear regressions were performed between internal knee mechanics and ACL graft tunnel locations andmore »angles for the patients with ACLR and the virtual ACLR models.


    Static and dynamic MRI revealed that a more vertical graft in the sagittal plane was significantly related ( P < .05) to a greater laxity compliance index ( R2= 0.40) and greater anterior tibial translation and internal tibial rotation during active knee extension ( R2= 0.22 and 0.23, respectively). Similarly, knee extension simulations with the virtual ACLR models revealed that a more vertical graft led to greater laxity compliance index, anterior translation, and internal rotation ( R2= 0.56, 0.26, and 0.13). These effects extended to simulations of walking, with a more vertical ACL graft inducing greater anterior tibial translation, ACL loading, and posterior migration of contact on the tibial plateaus.


    This study provides clinical evidence from patients who underwent ACLR and from complementary modeling that functional postoperative knee mechanics are sensitive to graft tunnel locations and graft angle. Of the factors studied, the sagittal angle of the ACL was particularly influential on knee mechanics.

    Clinical Relevance:

    Early-onset osteoarthritis from altered cartilage loading after ACLR is common. This study shows that postoperative cartilage loading is sensitive to graft angle. Therefore, variability in graft tunnel placement resulting in small deviations from the anatomic ACL angle might contribute to the elevated risk of osteoarthritis after ACLR.

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