Arthritis Foundation Research Articles

Disease Activity and Patient-Reported Health Measures in Relation to Cytokine Levels in Ankylosing Spondylitis.

IntroductionAnkylosing spondylitis (AS) is a lifelong condition where spinal inflammation causes chronic back pain and restriction of spinal function. While proinflammatory cytokines participate in the disease process, their relation with disease activity, spinal function, and quality of life is less well understood.MethodsCross-sectional study of serum levels of four inflammatory cytokines (IL-6, TNF, IL-23, and IL-17A) in AS patients not on biologics. Disease characteristics and simultaneous spinal function tests and patient-reported health measures (Bath Functional Index (BASFI), Dougados Functional Index (DFI), Modified Health Assessment Questionnaire (MHAQ), and routine laboratory parameters were recorded. The composite ASDAS-CRP score was used to classify disease activity as absent, low, or high.ResultsIn 164 AS patients (age 46 years, 70.1% males, 90.9% HLAB27 positive, ASDAS-CRP 1.8), disease activity was classified as inactive in 14%, low in 54%, and high in 31%. ASDAS-CRP correlated well with MHAQ, DFI, BASFI, and spinal mobility across patients with low and high disease activity (all p < 0.05). Cytokine levels did not correlate with ASDAS-CRP, ESR, BASFI, or spinal mobility scores and were comparable between patients with no, low, or high disease activity regardless of gender or disease duration (all p > 0.2).ConclusionsA large proportion of AS not on biologics have active disease far into the disease course. This impacts negatively on quality of life, work ability, and spinal mobility. Serum cytokine levels are poor markers for these central disease features in AS management.FundingAbbott Norway AS and Arthritis Foundation of Western Australia.Electronic supplementary materialThe online version of this article (10.1007/s40744-019-0161-7) contains supplementary material, which is available to authorized users.

Most Important Frequently Asked Questions From Patients With Hip or Knee Osteoarthritis: A Best‐Worst Scaling Exercise

To collect and prioritize the frequently asked questions (FAQs) that patients with hip or knee osteoarthritis (OA) and health care professionals consider to be the most important; to identify informational needs that go beyond guideline recommendations. FAQs were collected among health care professionals and from the arthritis helpline of the Dutch Arthritis Foundation. After deleting overlapping FAQs, the remaining FAQs were prioritized by patients and health care professionals using a maximum difference scaling method. A hierarchical Bayesian method was used to calculate relative importance scores. Differences between health care professionals and patients were analyzed using independent t-tests. A total of 28 health care professionals and the arthritis helpline provided 192 FAQs. After deleting overlapping FAQs, 60 FAQs were prioritized by 94 patients (57 [60.6%] women, mean age 67.3 years) and 122 health care professionals (67 [54.9%] women, mean age 45.7 years). The FAQ "What can I do myself to decrease symptoms and to prevent the OA from getting worse?" was prioritized as the most important by both patients and professionals. FAQs that were highly prioritized by patients but significantly different from professionals were more directed toward treatment options offered by health care professionals, whereas highly prioritized FAQs of professionals were more often focused on treatment options involving self-management. The health care professionals' perspective on informational needs differs from that of OA patients. These differences are important to address in order to achieve more active involvement of patients in their own treatment process.

Arthritis Awareness Month - May 2019.

Arthritis Awareness Month, led by the Arthritis Foundation (https://www.arthritis.org), is observed each May to bring attention to arthritis and its impact. Arthritis affects an estimated 54.4 million U.S. adults, or approximately one in four (1); and of these adults with arthritis, approximately 27% have severe joint pain (2). Arthritis also is linked to higher rates of physical inactivity (1).

Stephen I Katz: influential director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the US National Institutes of Health

Credit: NIAMS Steve Katz’s selection to be director of the US National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) in 1995 generated some...

Editorial introductions

Editorial introductions

Analgesic Use in Dutch Patients With Osteoarthritis: Frequent But Low Doses.

The aim of this study was to examine which analgesics are used by patients with osteoarthritis (OA)-related pain and how the analgesics are used in the preceding month. In addition, their beliefs about (pain) medication and the rationale of those declining to use analgesics were explored. An online cross-sectional survey was sent to 1521 patients participating in the panel of the Dutch Arthritis Foundation. Descriptive analyses and logistic regression were used to analyze data. Of the 842 participants (56%) with OA that responded, 70% had generalized OA, 26% had concomitant fibromyalgia, and 34% had another musculoskeletal morbidity. Of all participants, 71% used analgesics, and 34% used more than 1 type. Analgesics were used for more than 14 days in the preceding month by most participants, with paracetamol being used most frequently (51%). Doses used were predominantly lower than the daily defined dose: 58.2% for paracetamol, 31.2% for nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors, and 75.7% for weak opioids. Compared with participants with concomitant fibromyalgia or other musculoskeletal morbidities, participants with OA alone significantly more frequently declined to use analgesics (p < 0.01) and significantly less frequently used 2 or 3 types of analgesics (p < 0.05). In this population with generalized OA and musculoskeletal comorbidities, medication use was high, and more than 1 type of analgesic was frequently used. Patients with concomitant fibromyalgia or other musculoskeletal morbidities more frequently used 2 or 3 types of analgesics; however, this use was often intermittent and in low doses. Medication use on a daily basis and at higher doses may lead to improved analgesic effect.

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS William J. McCuneWilliam J. McCuneDr McCune is a graduate of Harvard College and the University of Cincinnati Medical School, USA. Following residency at the University of Michigan and fellowship at Brigham and Women's Hospital, USA, he joined the faculty of the University of Michigan, USA, where he is the Michael and Marcia Klein Professor of Rheumatic Diseases and Director of the Lupus Program. Dr McCune has devoted much of his research career to systemic lupus. He reported the clinical and immunologic effects of monthly bolus cyclophosphamide for severe lupus using methods that were subsequently adopted as standard treatment for lupus nephritis. He has since focused on improving the efficacy and safety of immunosuppressive therapy, including the use of leuprolide for ovarian protection in women receiving cyclophosphamide. His work in medical imaging helped establish the importance of MRI in neurological complications of lupus and rheumatoid arthritis, and he was the first to describe ultrasound imaging of articular cartilage. His current interests include the pathogenesis of cardiovascular disease in SLE, advanced MRI in SLE, and detailed population-based epidemiologic studies of the SLE in southeastern Michigan. Jon T. GilesJon T. GilesDr Giles's research interests are centered primarily within the inflammatory arthritides. His current projects center around understanding the inflammatory and non-inflammatory determinants of body composition abnormalities in rheumatoid arthritis and psoriatic arthritis, and their subsequent effects on health outcomes. Other current and past research involves the investigation of accelerated atherosclerosis and myocardial dysfunction in rheumatoid arthritis patients, understanding the determinants of rheumatoid arthritis-associated interstitial lung disease, and exploring the musculoskeletal side-effects of a class of medications used to suppress estrogen in women with certain forms of breast cancer. He is the recipient of grant support from the National Institutes of Health, the Arthritis Foundation, the Rheumatology Research Foundation, the Marianne Legato Foundation, and the Arthritis National Research Foundation.

Editorial introductions

Editorial introductions

Analgesic Effect of Viddha, A Nonpharmacological, CostEffective Local Therapy of Ayurveda (An Indian System of Medicine) in Knee Osteoarthritis (OA): A Case Report

Objective: Global statistics reveal over 100 million people worldwide suffer from OA, which is one of the most common causes of disability. According to the Arthritis Foundation, one in every two will develop symptoms of knee OA during their lives. One of the primary symptoms of persons with knee osteoarthritis is pain. The objective of this case report is to introduce Viddha, a non drug, local therapy from Ayurveda, an Indian System of Medicine as an intervention to achieve significant analgesia immediately, which is cost effective, has no side effects with possibility of arresting the progression of disease based on Ayurveda principle. Method and Result:-Viddhachikitsa(Viddha treatment)was done with the help of 26 gauge half inch short, fine, brown hypodermic needle.Its first sitting (done on 28^th Nov2017) provided immediate pain relief up to 60%in a female patient aged 47yrs with moderate Knee OA radiologically and severe symptomatically. In next two sittings (done on 30^th Nov and 4^th Dec 2017) there was 65% pain relief. Pain relief lasted till last follow up on 9^th Jan 2018. WOMAC index LK3.1on initial assessment before treatment was 88 which came down to 40 after treatment. Conclusion:-Viddha has therapeutic value in the treatment of Knee OA.

Evaluating quality of care in rheumatoid arthritis: the patient perspective

As rheumatoid arthritis (RA) is a potentially disabling disease, affecting up to 1% of the population, structural monitoring of standardised outcomes to identify best healthcare practices is vital to quality...

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS W. Joseph McCuneW. Joseph McCuneDr Joseph McCune is a graduate of Harvard College, and the University of Cincinnati Medical School, USA. Following residency at the University of Michigan, USA, and fellowship Brigham and Women's Hospital, USA, he joined the faculty of the University of Michigan, where he is the Michael and Marcia Klein Professor of Rheumatic Diseases and Director of the Lupus Program. Dr McCune has devoted much of his research career to systemic lupus. He reported the clinical and immunologic effects of monthly bolus cyclophosphamide for severe lupus using methods that were subsequently adopted as standard treatment for lupus nephritis and has since focused on improving the efficacy and safety of immunosuppressive therapy, including the use of leuprolide for ovarian protection in women receiving cyclophosphamide. His work in medical imaging helped establish the importance of MRI in neurological complications of lupus and rheumatoid arthritis, and he was the first to describe ultrasound imaging of articular cartilage. Current interests include the pathogenesis of cardiovascular disease in SLE, advanced MRI in SLE, and detailed population-based epidemiologic studies of the SLE in southeastern Michigan. Jon T. GilesJon T. GilesDr Giles's research interests are centered primarily within the inflammatory arthritides. Current projects center around understanding the inflammatory and non-inflammatory determinants of body composition abnormalities in rheumatoid arthritis and psoriatic arthritis, and their subsequent effects on health outcomes. Other current and past research involve the investigation of accelerated atherosclerosis and myocardial dysfunction in rheumatoid arthritis patients, understanding the determinants of rheumatoid arthritis-associated interstitial lung disease, and exploring the musculoskeletal side-effects of a class of medications used to suppress estrogen in women with certain forms of breast cancer. He is the recipient of grant support from the National Institutes of Health, the Arthritis Foundation, the Rheumatology Research Foundation, the Marianne Legato Foundation, and the Arthritis National Research Foundation.

Readability, Relevance and Quality of the Information in Spanish on the Web for Patients With Rheumatoid Arthritis

BackgroundEducation is a major health determinant and one of the main independent outcome predictors in rheumatoid arthritis (RA). The use of the Internet by patients has grown exponentially in the last decade. ObjectiveTo assess the characteristics, legibility and quality of the information available in Spanish in the Internet regarding to rheumatoid arthritis. Material and methodsThe search was performed in Google using the phrase rheumatoid arthritis. Information from the first 30 pages was evaluated according to a pre-established format (relevance, scope, authorship, type of publication and financial objective). The quality and legibility of the pages were assessed using two validated tools, DISCERN and INFLESZ respectively. Data extraction was performed by senior medical students and evaluation was achieved by consensus. ResultsThe Google search returned 323 hits but only 63% were considered relevant; 80% of them were information sites (71% discussed exclusively RA, 44% conventional treatment and 12% alternative therapies) and 12.5% had a primary financial interest. 60% of the sites were created by nonprofit organizations and 15% by medical associations. Web sites posted by medical institutions from the United States of America were better positioned in Spanish (Arthritis Foundation 4th position and American College of Rheumatology 10th position) than web sites posted by Spanish speaking countries. ConclusionsThere is a risk of disinformation for patients with RA that use the Internet. We identified a window of opportunity for rheumatology medical institutions from Spanish-speaking countries to have a more prominent societal involvement in the education of their patients with RA.

In memoriam: Wayne Akeson, MD (1928-2016).

In memoriam: Wayne Akeson, MD (1928-2016).

Community-Based Healthy Aging Interventions for Older Adults with Arthritis and Multimorbidity.

Examine the impact of programs led by community health workers on health and function in older adults with arthritis and other health conditions. We conducted a cluster-randomized trial of the Arthritis Foundation Exercise Program (AFEP) enhanced with the "10 Keys"™ to Healthy Aging compared with the AFEP program at 54 sites in 462 participants (mean age 73 years, 88 % women, 80 % white). Trained Community health workers delivered the 10-week programs. Outcomes assessed after 6 months included physical performance [Short Physical Performance Battery (SPPB)], Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, and preventive health behaviors. Both groups experienced improvements. Performance improved by 0.3 SPPB points in the AFEP/"10 Keys"™ group and 0.5 in AFEP alone; WOMAC scores declined by 3.0 and 3.9 points respectively. More participants had controlled hypertension at 6 months in both groups (60.1 % baseline to 76.7 % in AFEP/10 Keys and from 76.5 to 84.9 % in AFEP alone) and greater diabetes control (from 15.0 to 34.9 and 15.5 to 34.1 %, respectively). These community-based programs showed similar improvements in preventive health, mobility and arthritis outcomes.

Incorporating Novel Mobile Health Technologies Into Management of Knee Osteoarthritis in Patients Treated With Intra-Articular Hyaluronic Acid: Rationale and Protocol of a Randomized Controlled Trial.

BackgroundOsteoarthritis (OA) of the knee is one of the leading causes of disability in the United States. One relatively new strategy that could be helpful in the management of OA is the use of mHealth technologies, as they can be used to increase physical activity and promote exercise, which are key components of knee OA management.ObjectiveCurrently, no published data on the use of a mHealth approach to comprehensively monitor physical activity in patients with OA are available, and similarly, no data on whether mHealth technologies can impact outcomes are available. Our objective is to evaluate the effectiveness of mHealth technology as part of a tailored, comprehensive management strategy for patients with knee OA.MethodsThe study will assess the impact of a smartphone app that integrates data from a wearable activity monitor (thereby both encouraging changes in mobility as well as tracking them) combined with education about the benefits of walking on patient mobility. The results from the intervention group will be compared with data from a control group of individuals who are given the same Arthritis Foundation literature regarding the benefits of walking and wearable activity monitors but who do not have access to the data from those monitors. Activity monitors will capture step count estimates and will compare those with patients’ step goals, calories burned, and distance walked. Patients using the novel smartphone app will be able to enter information on their daily pain, mood, and sleep quality. The relationships among activity and pain, activity and mood, and sleep will be assessed, as will patient satisfaction with and adherence to the mobile app.ResultsWe present information on an upcoming trial that will prospectively assess the ability of a mobile app to improve mobility for knee OA patients who are treated with intra-articular hyaluronic acid.ConclusionsWe anticipate the results of this study will support the concept that mHealth technologies provide continuous, real-time feedback to patients with OA on their overall level of activity for a more proactive, personalized approach to treatment that may help modify behavior and assist with self-management through treatment support in the form of motivational messages and reminders.

Take Charge of Pain: evaluating a community-targeted self-management education program for people with musculoskeletal pain.

Issue addressed Musculoskeletal conditions are highly prevalent, affecting 28% of the Australian population. Given the persistent nature of many musculoskeletal conditions self-management is recognised as an important aspect of effective disease management. However, participant recruitment and retention for formal self-management programs is a challenge. Methods Arthritis SA (Arthritis Foundation of South Australia, a non-profit community health organisation) redesigned a shorter, community-orientated self-management education program delivered by health professionals. The program utilises aspects of the Stanford model of chronic disease self-management and motivational interviewing as well as principles of adult learning to create an effective learning environment. The program aims to guide participants to learn and practise a range of pain management strategies that are known to be effective in improving quality of life. This study used a pre- and post-test (at 6 weeks) design to determine whether this program achieved benefits in self-reported health outcomes. Outcomes that were measured included pain, fatigue, health distress, self-efficacy and communication. Results A response rate of 47% (n=102) was achieved and small but statistically significant improvements in mean [s.d.] pain scores (6.1 [2.3] to 5.4 [2.4], P=0.001), health distress (2.3 [1.3] to 2.0 [1.3], P=0.002) and self-efficacy (6.2 [2.1] to 6.8 [2.2], P=0.002) were found. Conclusion Community-based participants of this shorter, focused program recorded small but significant improvements in self-reported pain, health distress and self-efficacy. For those who completed the current program, Arthritis SA is currently exploring the potential of developing a booster session to promote sustainable positive health outcomes. So what? Supporting self-management through education is recognised as important but also as a key challenge for effective management of musculoskeletal conditions. Using a pre-post evaluation design, this study demonstrated effectiveness (short-term improvements for self-reported pain, health distress and self-efficacy) for a redesigned and shortened community-targeted program focusing on musculoskeletal pain.

Legibilidad, relevancia y calidad de la información en español en la Web para pacientes con artritis reumatoide

BackgroundEducation is a major health determinant and one of the main independent outcome predictors in rheumatoid arthritis (RA). The use of the Internet by patients has grown exponentially in the last decade. ObjectiveTo assess the characteristics, legibility and quality of the information available in Spanish in the Internet regarding to rheumatoid arthritis. Material and methodsThe search was performed in Google using the phrase rheumatoid arthritis. Information from the first 30 pages was evaluated according to a pre-established format (relevance, scope, authorship, type of publication and financial objective). The quality and legibility of the pages were assessed using two validated tools, DISCERN and INFLESZ respectively. Data extraction was performed by senior medical students and evaluation was achieved by consensus. ResultsThe Google search returned 323 hits but only 63% were considered relevant; 80% of them were information sites (71% discussed exclusively RA, 44% conventional treatment and 12% alternative therapies) and 12.5% had a primary financial interest. 60% of the sites were created by nonprofit organizations and 15% by medical associations. Web sites posted by medical institutions from the United States of America were better positioned in Spanish (Arthritis Foundation 4th position and American College of Rheumatology 10th position) than web sites posted by Spanish speaking countries. ConclusionsThere is a risk of disinformation for patients with RA that use the Internet. We identified a window of opportunity for rheumatology medical institutions from Spanish-speaking countries to have a more prominent societal involvement in the education of their patients with RA.

The Role of Caveolin-1 in Intervertebral Disc Degeneration and Regeneration

Introduction During intervertebral disc (IVD) degeneration, the main cell type in the nucleus pulposus (NP) shifts from notochordal cells (NCs) to chondrocyte-like cells (CLCs). Microarray analysis revealed that caveolin-1 expression was correlated with IVD degeneration. The aim of this study was to determine the role of caveolin-1 in NC and CLC physiology to assess its potential role in IVD regeneration. Material and Methods Protein expression (caveolin-1, apoptosis, progenitor cell markers, extracellular matrix, TGF-β-signaling pathway) was determined in IVDs of wild type (WT) and caveolin-1 knockout (KO) mice and canine IVDs of different degeneration grades (immunofluorescence, immunohistochemistry, TUNEL assay). Micro-aggregate cultures of CLCs from canine and human degenerated IVDs (Thompson grade III) were treated with chondrogenic medium (incl. TGF-β1) alone or in combination with (a) caveolin-1 scaffolding domain peptide (CSD) and/or (b) siRNA against caveolin-1. DNA, glycosaminoglycan (GAG) content, collagen type I and II immunohistochemistry and gene expression profiling (RT-qPCR) for extracellular matrix production/degradation-, cell proliferation- and apoptosis markers was performed. Results The NP of WT mice was rich in viable NCs, whereas the NP of caveolin-1 KO mice contained more collagen type II-rich matrix and less cells together with an increased progenitor cell surface marker (Tie2+/GD2+) expression and a higher apoptotic activity. Caveolin-1 expression increased in the later stages of canine IVD degeneration, together with a significantly increased apoptotic activity. Caveolin-1 knockdown significantly decreased GAG deposition in the CLC aggregates (6–14%), whereas CSD treatment significantly rescued and increased GAG deposition (11–16%). Conclusion Caveolin-1 plays a crucial role in preservation of NCs, underscored by the NP phenotype of caveolin-1 KO mice. Caveolin-1 may be related with cell senescence given its increased expression in degenerated IVDs. However, caveolin-1 knockdown decreased extracellular matrix production, while CSD supplementation rescued this effect. The latter implies that CSD may be a useful disease modifying agent since it is known to influence degeneration-related signaling pathways (incl. TGF-β signaling). Altogether, this indicates that the increased caveolin-1 expression during IVD degeneration may also be a repair mechanism rather than being merely a senescence marker. Acknowledgment This work was supported by AOSpine Research Network grants (SRN2011_11, AOSPINE 106540) and the Dutch Arthritis Foundation (LLP22).

The Effect of Bone Morphogenetic Protein-2 on Chondrocyte-like Cells Derived from Degenerated Human and Canine Intervertebral Discs

Introduction Both humans and dogs experience low back pain, which is related to intervertebral disc (IVD) degeneration. Biologic repair of the degenerated IVD is mainly based on growth factors that exert anabolic matrix effects, and mesenchymal stromal cells (MSCs) to replenish the cell population of the degenerated IVD. Thus far, the anabolic effects of different growth factors have not been compared. The aim of this study was to study the effect of the frequently used growth factors transforming growth factor β 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) on canine and human chondrocyte-like cells (CLCs) from degenerated IVDs alone and in combination with MSCs. Material and Methods CLCs from degenerated human, canine chondrodystrophic (CD) and non-chondrodystrophic (NCD) IVDs (Thompson score III) were cultured in micro-aggregates in base culture medium (negative control), or supplemented with TGF-β1 (10 ng/mL) or BMP-2 (100 or 250 ng/mL) for 28 days. The additive effect of MSCs was studied in CD CLCs. Canine male CD CLCs were cultured in an albumin-based hydrogel (3*106 cells/mL) with or without the addition of female bone marrow-derived MSCs (BMSCs) (CLC:BMSC 1:1) in control or 250 ng/mL BMP-2-supplemented culture medium for 28 days. Read out parameters were extracellular matrix (ECM) production (RT-qPCR, glycosaminoglycan (GAG) production, Safranin O/Fast Green staining, immunohistochemistry), cell proliferation (DNA content, RT-qPCR) and apoptosis (RT-qPCR). Results TGF-β1 treatment increased GAG deposition in human and canine CLC micro-aggregates, but also induced collagen type I deposition and a fibrotic rim. The latter was not observed in BMP-2-treated micro-aggregates. 250 ng/mL BMP-2 was more potent than 100 ng/mL BMP-2 in increasing GAG deposition and DNA content in canine and human micro-aggregates. Similarly, in the hydrogel culture system, BMP-2 induced GAG and collagen type II deposition and a higher DNA content compared with untreated controls. DNA and GAG content of BMSC+CLC hydrogels was higher than hydrogels with CLCs alone in the absence of BMP-2. In the BMP-2-treated hydrogels, DNA content of BMSC+CLC was higher than hydrogels with CLCs alone; GAG deposition or release was comparable between BMSC+CLC and CLC alone in the presence of BMP-2. Conclusion In two different 3D culture systems, BMP-2 exerted comparable regenerative effects as TGF-β1 on human and canine CLCs in terms of GAG deposition and cell proliferation, but BMP-2 did not induce fibrotic (re)differentiation as observed with TGF-β1 treatment. Moreover, in the BMP-2-treated BMSC:CLC-containing hydrogels, where only half of the amount of CLCs were seeded compared with CLC alone, the DNA content was higher and an equal amount of GAGs was deposited, indicating that the BMSCs exerted an additional, regenerative effect in addition to BMP-2 treatment. PCR for SRY:GAPDH genes on DNA will indicate the ratio male(CLCs):female(BMSCs) present at the end of the study. This will indicate whether the BMSCs exerted trophic effects or chondrogenically differentiated. Acknowledgments This work was supported by an AOSpine Research Network grant (SRN2011_11) and the Dutch Arthritis Foundation (LLP22).

The Species-Specific Regenerative Effect of Notochordal Cell-conditioned Medium on Degenerated Human Nucleus Pulposus Cells

Introduction During human intervertebral disc (IVD) degeneration, the main cell type shifts from notochordal cells (NCs) to nucleus pulposus cells (NPCs). NCs secrete factors with regenerative potential, making them an interesting focus for regenerative strategies. Research into these strategies employs non-human donors due to easy availability of their NC-rich nucleus pulposus (NP) tissue. To determine the feasibility of translating these strategies toward clinical application, this study aimed to delineate whether NC-secreted factors of different species have a cross-species regenerative effect on degenerated human NPCs. Material and Methods Healthy human, porcine and canine NC-rich NP tissues (derived from Thompson grade I IVDs) were compared by histology, collagen, DNA and glycosaminoglycan (GAG) content per mg wet tissue weight. NP tissue of each species was cultured for 4 days and NC-conditioned medium (NCCM) was collected. Human NPC micro-aggregates from degenerated IVDs (Thompson grade III) were cultured for 28 days in human, canine or porcine NCCM. GAG content (corrected for DNA) was determined, and Safranin O/Fast Green staining, collagen type I, II and X IHC and gene expression profiling were performed. Results Canine and porcine NPs were richer in NCs than human NPs. Human NPs contained the highest collagen content, whereas the DNA and GAG content of canine NPs was significantly higher than human or porcine NPs. NCCM from all species significantly increased the DNA and GAG content of the human NPC micro-aggregates. Porcine and canine NCCM were significantly more potent than human NCCM in inducing GAG deposition, whereas only human NCCM induced collagen type II production. Conclusion Secreted factors from human, canine and porcine NC-rich NPs exerted regenerative effects on human NPCs, indicating a cross-species effect. The species-specific NP properties appear to influence the regenerative capacity of NCCM on human NPCs. Bioactive compound(s) with treatment potential for human IVD degeneration are present in NCCM of different species, implying that strategies based on NC-technology employing canine or porcine models have potential for successful translation into humans. Acknowledgments This work was supported by an AOSpine Research Network grant (SRN2011_11) and the Dutch Arthritis Foundation (LLP22).