The Rising Incidence of Degenerative and Posttraumatic Osteoarthritis of the Knee in the United States Military

Showery, James; Kusnezov, Nicholas; Dunn, John C.; Bader, Julia; Belmont, Philip J.; Waterman, Brian R.

doi:10.1016/j.arth.2016.03.026

Cited by 83 publications

(71 citation statements)

References 36 publications

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“…Despite the increasing incidence of PTOA in both military and civilian populations, the exact mechanisms connecting joint trauma to the onset and progression of joint degeneration are poorly understood. Evidence supporting the existence of underlying acute biologic phenomena at the time of ACL injury that precipitate rapid joint degeneration continues to emerge .…”

Section: Discussionmentioning

confidence: 99%

Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post‐traumatic osteoarthritis

Maerz

Sherman

Newton

et al. 2018

Journal Orthopaedic Research

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ACL rupture is a major risk factor for post-traumatic osteoarthritis (PTOA) development. Little information exists on acute systemic metabolic indicators of disease development. Thirty-six female Lewis rats were randomized to Control or noninvasive anterior cruciate ligament rupture (ACLR) and to three post-injury time points: 72 h, 4 weeks, 10 weeks (n = 6). Serum was collected and analyzed by H nuclear magnetic resonance (NMR) spectroscopy and combined direct injection and liquid chromatography (LC)-mass spectrometry (MS)/MS (DI-MS). Univariate and multivariate statistics were used to analyze metabolomic data, and predictive biomarker models were analyzed by receiver operating characteristic (ROC) analysis. Topological pathway analysis was used to identify perturbed pathways. Two hundred twenty-two metabolites were identified by H NMR and DI-MS. Differences in the serum metabolome between ACLR and Control were dominated by medium- and long-chain acylcarnitine species. Further, decreases in several tryptophan metabolites were either found to be significantly different in univariate analysis or to play important contributory roles to multivariate model separation. In addition to acylcarnitines and tryptophan metabolites, glycine, carnosine, and D-mannose were found to differentiate ACLR from Control. Glycine, 9-hexadecenoylcarnitine, trans-2-Dodecenoylcarnitine, linoelaidyl carnitine, hydroxypropionylcarnitine, and D-Mannose were identified as biomarkers with high area under ROC curve values and high predictive accuracies. Our analysis provides new information regarding the potential contribution of inflammatory processes and immune dysregulation to the onset and progression of PTOA following ACL injury. As these processes have most commonly been associated with inflammatory arthropathies, larger-scale studies elucidating their involvement in PTOA development and progression are necessary. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1969-1979, 2018.

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Section: Discussionmentioning

confidence: 99%

Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post‐traumatic osteoarthritis

Maerz

Sherman

Newton

et al. 2018

Journal Orthopaedic Research

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“…Thus, articular cartilage is at high risk of damage during initial trauma and, if left untreated, may results in lesions in the underlying subchondral bone, leading to biomechanics and homeostasis disturbances in the knee as a whole. This process may result in loss of mobility, wear and arthritis (9,10).…”

Section: Introductionmentioning

confidence: 99%

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

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“…Like idiopathic OA seen in older individuals, PTOA causes pain, impaired function, and overall decreased quality of life, but PTOA secondary to ACL injuries can affect a much younger population who are otherwise healthy. Investigating how ACL injuries lead to PTOA may have important implications for these young individuals who may face significant cartilage degeneration as a sequelae in the future …”

mentioning

confidence: 99%

Longitudinal analysis of tibiofemoral cartilage contact area and position in ACL reconstructed patients

Chen

Amano

Pedoia

et al. 2018

Journal Orthopaedic Research

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Patients who have suffered ACL injury are more likely to develop early onset post-traumatic osteoarthritis despite reconstruction. The purpose of our study was to evaluate the longitudinal changes in the tibiofemoral cartilage contact area size and location after ACL injury and reconstruction. Thirty-one patients with isolated unilateral ACL injury were followed with T weighted Fast Spin Echo, T and T MRI at baseline prior to reconstruction, and 6 months, 1 year, and 2 years after surgery. Areas were delineated in FSE images with an in-house Matlab program using a spline-based semi-automated segmentation algorithm. Tibiofemoral contact area and centroid position along the anterior-posterior axis were calculated along with T and T relaxation times on both the injured and non-injured knees. At baseline, the injured knees had significantly smaller and more posteriorly positioned contact areas on the medial tibial surface compared to corresponding healthy knees. These differences persisted 6 months after reconstruction. Moreover, subjects with more anterior medial centroid positions at 6 months had elevated T and T measures in the posterior medial tibial plateau at 1 year. Changes in contact area and centroid position after ACL injury and reconstruction may characterize some of the mechanical factors contributing to post-traumatic osteoarthritis. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2718-2727, 2018.

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The Rising Incidence of Degenerative and Posttraumatic Osteoarthritis of the Knee in the United States Military

Cited by 83 publications

References 36 publications

Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post‐traumatic osteoarthritis

Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post‐traumatic osteoarthritis

Macrophage: A Potential Target on Cartilage Regeneration

Longitudinal analysis of tibiofemoral cartilage contact area and position in ACL reconstructed patients

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