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Tuhina Neogi, MD, PhD

@tuhinaneogi.bsky.social
1.2K followers 887 following 39 posts

Rheumatologist & Epidemiologist Researcher in #osteoarthritis & #gout | Prof. of Medicine & Epidemiology | Chief of Rheumatology | 🇨🇦 | Boston University Chobanian & Avedisian School of Medicine & Boston Medical Center #RheumSky #MedSky #Rheumatology

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Reposted by Tuhina Neogi, MD, PhD
Jamie Collins @colljamie.bsky.social · 14/01/2026
Exciting opportunity to work with Multicenter #Osteoarthritis Study (MOST) data!
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Tuhina Neogi, MD, PhD @tuhinaneogi.bsky.social · 14/01/2026
We're excited 🎉 to share a new *pilot grant* 💰 opportunity from the Multicenter #Osteoarthritis Study (MOST). Application deadline 📆: April 6, 2026. Please share 🗣️. @bu-bmc-rheum.bsky.social @profdeepakkumar.bsky.social
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Reposted by Tuhina Neogi, MD, PhD
Kelsey H. Collins @kelseyhcollins.bsky.social · 03/12/2025
Honored to share our new paper, Osteoarthritis as a Systemic Disease, in @natrevrheum.nature.com, out today: rdcu.be/eSXLW - thanks to Ida Haugen, @tuhinaneogi.bsky.social and @farsh-g.bsky.social for your input on gaps and opportunities.
rdcu.be
Osteoarthritis as a systemic disease
Nature Reviews Rheumatology - Emerging evidence suggests a paradigm shift in viewing osteoarthritis (OA) as a systemic, bidirectional disease. This Review examines the current data supporting this...
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Tuhina Neogi, MD, PhD @tuhinaneogi.bsky.social · 11/11/2025
Taking a moment to remember on 11/11
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Tuhina Neogi, MD, PhD @tuhinaneogi.bsky.social · 23/10/2025
Great start to #GCAN2025 with strong representation from STOP-Gout trial, fun great debate (with hats), proud of mentee presentations, & great to see collaborators in person with #Burt @rheumcat.bsky.social @nicoladalbeth.bsky.social
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 20/08/2025
Thanks to @medscape.com for highlighting our work www.medscape.com/viewarticle/...
medscape.com
Calcium Deposition Can Increase Osteoarthritis Risk
A new analysis suggests that chondrocalcinosis is a cause, rather than just a consequence, of knee osteoarthritis.
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 20/08/2025
Our #Methodology #JournalClub returns on September 3, 2025 at 12:15pm ET with Dr. Vijaya Kolachalama leading a discussion on his work with PodGPT Register here: bostonu.zoom.us/meeting/regi... Article here: pubmed.ncbi.nlm.nih.gov/40636401/
Boston MCRC Monthly Methodology Journal Club
Wednesday, September 3, 2025 at 12:15am
PodGPT: an audio augmented large language model for research and education
Presenter Vijaya Kolachalama, PhD FAHA
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 12/09/2025
New publication led by BMC Brighton Internal Medicine residency Dr. Angela Achkar with @spondymd.bsky.social @rheumcat.bsky.social trebuchet.public.springernature.app/get_content/...
Targeted and biologic therapies and risk of total knee or hip
replacement in axial spondyloarthritis and psoriatic arthritis

Angela Achkar
Christine Peloquin
Jean W. Liew
Maureen Dubreuil
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 17/09/2025
Article here: www.acpjournals.org/doi/10.7326/...
acpjournals.org
High Tibial Osteotomy for Medial Compartment Knee Osteoarthritis: A Randomized Trial With Parallel Preference Arm: Annals of Internal Medicine: Vol 178, No 9
Background: Medial opening wedge high tibial osteotomy (HTO) is a limb realignment surgery that aims to preserve joint structure and improve clinical outcomes by redistributing ambulatory loads on the...
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 17/09/2025
Join us for the second session in our Boston MCRC Monthly Methodology Journal Club series on October 1, 2025 at 12.15 pm ET. Dr. David Felson will present, followed by insights from our invited Guest Discussant, Dr. Trevor Birmingham. Register here: bostonu.zoom.us/meeting/regi...
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
We at BU Rheum had the pleasure of learning from Drs. Divya Shankar and Mari-Lynn Drainone to speak today on Implementation Science. sites.bu.edu/ciis/ @bu-bmc-rheum.bsky.social
sites.bu.edu
CIIS
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
💡Implementation science (IS) is the study of methods and strategies that facilitate uptake of evidence based interventions into routine practice.
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
✅ IS takes places following efficacy and effectiveness studies, within controlled settings and in practice. 3 types of hybrid IS studies: Type 1: primary aim is to determine effectiveness, Type 2: Codetermining effectiveness & feasibility, Type 3: focuses on implementation
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Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
IS uses conceptual frameworks to systematically understand why people do what they do (patients, clinicians, healthcare systems), how to operationalize an intervention, how to scale it and how to assess outcomes
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
🖼️Frameworks exist in 3 forms: (1) Process: how to plan and execute a strategy, (2) Determinant: factors that impede or enable the implementation process and (3) Evaluative: selection of outcomes to study
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
PARIHS is a determinant framework based on the concept that implementation is a function of: A. Evidence (research, clinical expertise, patient preferences), B. Context (setting, resources) and C. Facilitation through influence and relationships.
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
CFIR (consolidated framework for implementation research) is a determinant framework addresses the inner and outer settings, the implementation process, the innovation and the individuals’ roles and characteristics. implementationscience.biomedcentral.com/articles/10....
implementationscience.biomedcentral.com
The updated Consolidated Framework for Implementation Research based on user feedback - Implementation Science
Background Many implementation efforts fail, even with highly developed plans for execution, because contextual factors can be powerful forces working against implementation in the real world. The Consolidated Framework for Implementation Research (CFIR) is one of the most commonly used determinant frameworks to assess these contextual factors; however, it has been over 10 years since publication and there is a need for updates. The purpose of this project was to elicit feedback from experienced CFIR users to inform updates to the framework. Methods User feedback was obtained from two sources: (1) a literature review with a systematic search; and (2) a survey of authors who used the CFIR in a published study. Data were combined across both sources and reviewed to identify themes; a consensus approach was used to finalize all CFIR updates. The VA Ann Arbor Healthcare System IRB declared this study exempt from the requirements of 38 CFR 16 based on category 2. Results The systematic search yielded 376 articles that contained the CFIR in the title and/or abstract and 334 unique authors with contact information; 59 articles included feedback on the CFIR. Forty percent (n = 134/334) of authors completed the survey. The CFIR received positive ratings on most framework sensibility items (e.g., applicability, usability), but respondents also provided recommendations for changes. Overall, updates to the CFIR include revisions to existing domains and constructs as well as the addition, removal, or relocation of constructs. These changes address important critiques of the CFIR, including better centering innovation recipients and adding determinants to equity in implementation. Conclusion The updates in the CFIR reflect feedback from a growing community of CFIR users. Although there are many updates, constructs can be mapped back to the original CFIR to ensure longitudinal consistency. We encourage users to continue critiquing the CFIR, facilitating the evolution of the framework as implementation science advances.
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
Proctor’s Conceptual model spans the intervention 💡, strategies 🧩, outcomes 🛠️ and efficacy/effectiveness 📊. pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov
Outcomes for Implementation Research: Conceptual Distinctions, Measurement Challenges, and Research Agenda
An unresolved issue in the field of implementation research is how to conceptualize and evaluate successful implementation. This paper advances the concept of “implementation outcomes” distinct from s...
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 23/09/2025
🗣️ How might implementation science be applied in your field? Are there evidence-based interventions that need broader uptake?
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 30/09/2025
We were proud to support Dr. Ayesha Abdeen, Chief of Hip and Knee Arthroplasty at @bostonmedical.bsky.social, being awarded the Dr. Marian Ropes Award by the Arthritis Foundation
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Tuhina Neogi, MD, PhD @tuhinaneogi.bsky.social · 15/09/2025
Stop #1 on my Chicago roadtrip: C-COMP seminar at Rush MSK Pain Center mskpain.center, where we discussed pain sensitization as a trait versus state. And photo of me in my usual mid-speech contortion! Thanks to @jointsintheworld.bsky.social and @rem7106.bsky.social for hosting me!
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 06/09/2025
New publication led by BMC Internal Medicine graduate Dr. Navya George with @rheumcat.bsky.social @tuhinaneogi.bsky.social Does hsCRP provide insights into an inflammatory phenotype of knee osteoarthritis? authors.elsevier.com/sd/article/S...
Does hsCRP provide insights into an inflammatory
phenotype of knee osteoarthritis?

Navya George, Jean W. Liew, Na Wang, Sarah
Tilley, Ali Guermazi, John Lynch, Cora Lewis,
James Torner, Tuhina Neogi

Published in Osteoarthritis and Cartilage
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Reposted by Tuhina Neogi, MD, PhD
Rheum Cat @rheumcat.bsky.social · 07/08/2025
Radiographic chondrocalcinosis and the development of knee pain and knee OA: a collaboration with @curlygeneticist.bsky.social @tuhinaneogi.bsky.social ard.eular.org/action/showP...
ard.eular.org
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 07/08/2025
New publication from @rheumcat.bsky.social @tuhinaneogi.bsky.social in collaboration with @curlygeneticist.bsky.social ard.eular.org/action/showP...
Chondrocalcinosis and incident knee osteoarthritis:
findings from 2 large prospective cohorts with
20 years of follow-up

Yahong Wu, Jean W. Liew, Justin D. Boer, Maggie Westerland, Michael LaValley, Trudy Voortman, Sita Bierma-Zeinstra, Edwin H.G. Oei, Joyce B.J. van Meurs, Tuhina Neogi, Cindy G. Boer
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Tuhina Neogi, MD, PhD @tuhinaneogi.bsky.social · 04/08/2025
I was in non-stop meetings (as usual) and when I finally got to look at emails just now, I was excited to see that it was that time of year again: #ACR25 #EmailConfetti! Congratulations on everyone’s acceptances!
media.tenor.com
a bunch of colorful squares are flying in the air
ALT: a bunch of colorful squares are flying in the air
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Tuhina Neogi, MD, PhD @tuhinaneogi.bsky.social · 13/07/2025
Is it just me or did NIH Reporter just vanish from the internet??
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Reposted by Tuhina Neogi, MD, PhD
The European Alliance of Associations for Rheumatology @eular.org · 12/07/2025
Missed a session or want to revisit the highlights of #EULAR2025? 📺Access the On-Demand Congress Platform and relive from inspiring Scientific Sessions to the unforgettable Opening Ceremony 👉 pulse.ly/zbo1z5cmph 🗓️ Available from Monday 16 June until 31 December 2025 #Rheumatology
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Reposted by Tuhina Neogi, MD, PhD
Rheum Cat @rheumcat.bsky.social · 11/07/2025
For people living with arthritis: “Sharing your arthritis story is crucial to further understanding the potential patient impact of the passage of the One Big Beautiful Bill Act” www.votervoice.net/BroadcastLin...
votervoice.net
Action Center
Take action today - use the resources here to learn who your elected officials are, what opportunities we have to advocate from the comfort of your own home, federal and state legislation, and more!
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GUCDD MDPI @gucddmdpi.bsky.social · 10/07/2025
‪📢 New Publication! 📝 Effect of Allopurinol Use on Kidney Function Among Patients with Gout and Chronic Kidney Disease 👥 Ana Beatriz Vargas-Santos, Christine E. Peloquin, and @tuhinaneogi.bsky.social 🔗 Read: www.mdpi.com/2813-4583/3/... #gout #chronickidneydisease #renal #kidney #allopurinol
mdpi.com
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Reposted by Tuhina Neogi, MD, PhD
ACR Journals @acr-journals.bsky.social · 03/07/2025
Editorial in A&R "Kerschbaumer & colleagues have introduced a new issue to consider in evaluating large multicenter randomized trials, spotlighting the high rates of placebo response, rates that are threatening the ability to detect efficacy of rheumatic disease treatments." doi.org/10.1002/art....
"Kerschbaumer and colleagues have introduced a new issue to consider in evaluating large multicenter randomized trials, spotlighting the high rates of placebo response, rates that are threatening the ability to detect efficacy of rheumatic disease treatments."
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Reposted by Tuhina Neogi, MD, PhD
Nature Reviews Rheumatology @natrevrheum.nature.com · 05/06/2025
New content online:
bit.ly
Advances in the treatment of ANCA-associated vasculitis
Nature Reviews Rheumatology, Published online: 05 June 2025; doi:10.1038/s41584-025-01266-1This Review discusses the advances and challenges of managing antineutrophil cytoplasmic antibody-associated vasculitis. The authors discuss current treatment options, emerging therapies and unmet needs in the management of this disease.
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Reposted by Tuhina Neogi, MD, PhD
GUCDD MDPI @gucddmdpi.bsky.social · 06/06/2025
We are pleased to announce that GUCDD has received its first CiteScore! 📈 CiteScore [2024]: 1.4 🔗 For more information: www.scopus.com/sourceid/211... #CiteScore #GoutResearch #Rheumatology #Scopus
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 06/05/2025
You can view a summary of their presentation above and learn more about the program on our T32 Program Page: www.bumc.bu.edu/rheumatology.... For upcoming sessions, please visit our T32 Lecture Series Schedule: www.bumc.bu.edu/rheumatology..., and we encourage you to join us for the next event!
bumc.bu.edu
Boston University Rheumatology Research Training (BURRT) T32 Program | Rheumatology
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Reposted by Tuhina Neogi, MD, PhD
Dr. Curmudgeon @altgovdoc.altgov.info · 02/06/2025
Males and females process pain through different brain pathways. Current pain management has been directed to how males process pain. This might also explain why females suffer more from chronic pain. pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov
Self-regulated analgesia in males but not females is mediated by endogenous opioids
Converging lines of preclinical and clinical research indicate that females, in stark contrast to males, display an increased prevalence of chronic pain. Females also demonstrate weaker analgesic effi...
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Reposted by Tuhina Neogi, MD, PhD
ACR Journals @acr-journals.bsky.social · 03/06/2025
Phase 3 RCT in Chinese patients with gout showed dotinurad 4 mg/day was superior to febuxostat 40 mg/day in achieving serum urate levels ≤6.0 mg/dL at week 24. Treatment-emergent AE incidence was similar between treatment groups Arthritis & Rheumatology doi.org/10.1002/art.... #Medsky
Responder rate (serum urate ≤6.0 mg/dL) over time (full analysis set). LOCF, last observation carried forward
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 03/06/2025
This month we celebrate World Scleroderma Day. We’ll highlight the work BUMC does as a leader in Scleroderma care.
National Scleroderma Awareness Month
June

with teal ribbon
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Reposted by Tuhina Neogi, MD, PhD
ACR Journals @acr-journals.bsky.social · 02/06/2025
Welcome new Arthritis & Rheumatology Editor, S. Louis Bridges, Jr., MD, PhD! 🎉 We asked Dr. Bridges about his research background and exciting plans for his tenure at A&R youtu.be/q8wYr51IUFg
youtu.be
Welcome Incoming A&R Editor S. Louis Bridges, Jr.
YouTube video by American College of Rheumatology
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The Lancet Rheumatology @thelancetrheum.bsky.social · 30/05/2025
NEW RESEARCH—Long-term effectiveness of non-surgical interventions for chronic low back pain: a systematic review and meta-analysis bit.ly/43mmyCb Plus, linked Comment bit.ly/4dFiRej #Medsky #Rheumsky #Physiosky
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Tuhina Neogi, MD, PhD @tuhinaneogi.bsky.social · 20/05/2025
Trial of metformin for knee #osteoarthritis showed improvement in knee pain vs. placebo. What’s the mechanism? Curious to see what the weight loss differences were been groups. jamanetwork.com/journals/jam...
jamanetwork.com
Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity
This randomized clinical trial assesses the effect of metformin on knee pain among patients with symptomatic knee osteoarthritis and overweight or obesity.
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Reposted by Tuhina Neogi, MD, PhD
ACR Journals @acr-journals.bsky.social · 09/05/2025
New installment in the A&R immunology series describes 3 broad stages of acute inflammation in gout: initiation, leukocyte mobilization, & self-resolution, and examines the role of the NLRP3 inflammasome in acute MSU crystal-induced inflammation doi.org/10.1002/art.... #medsky #rheumsky #immunosky
Gout and NLRP3 inflammasome biology. Graphical abstract created with BioRender
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Tuhina Neogi, MD, PhD @tuhinaneogi.bsky.social · 02/05/2025
Thank you to UTSW Rheumatology for hosting me the past few days. I enjoyed meeting folks in Rheum & other Div/Depts, & engaging in micro-mentoring. I think I got people interested in #osteoarthritis, pain mechanisms, & #gout! I’m looking forward to new collaborations! @unamakris.bsky.social
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Maureen Dubreuil, MD MSc @spondymd.bsky.social · 01/04/2025
We found that diagnostic delay in axial spondyloarthritis was 21% longer (7 months) among people with a social need, using an accelerated failure time model. @jrheumatol.bsky.social @renatoferrandiz.bsky.social www.jrheum.org/content/52/4...
jrheum.org
Disparities in Time to Diagnosis of Radiographic Axial Spondyloarthritis
Objective Radiographic axial spondyloarthritis (r-axSpA) has a 7-year average diagnostic delay. Although the effects of sex or gender on time to diagnosis have been evaluated, the role of social deter...
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Reposted by Tuhina Neogi, MD, PhD
Maureen Dubreuil, MD MSc @spondymd.bsky.social · 03/04/2025
Congrats to Deepak Kumar sites.bu.edu/kumarlab/ who found that earlier PT and >12 sessions were associated with lower risk of future intra-articular therapy use in people w/ knee OA. doi.org/10.1002/art....
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Reposted by Tuhina Neogi, MD, PhD
Nature Reviews Rheumatology @natrevrheum.nature.com · 27/03/2025
✨April Issue✨| An update on the role of the immune system in osteoarthritis, including mechanisms, challenges and future directions @boutetmarieastrid.bsky.social @JeremieSellam @larhumato.bsky.social @jeromeguicheux.bsky.social #Rheumsky #Medsky bit.ly/3FEMv6q
bit.ly
The role of the immune system in osteoarthritis: mechanisms, challenges and future directions - Nature Reviews Rheumatology
This Review provides an update on the role of innate and adaptive immune cells in the pathogenesis of osteoarthritis. The authors discuss emerging therapeutics that target the immune system in osteoar...
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 26/03/2025
Now with publication-ready formatting, our group's paper entitled Relationship between knee pain and depth-specific measures of proximal tibial subchondral bone density authors.elsevier.com/c/1kq8u3npMr...
authors.elsevier.com
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Rheum Cat @rheumcat.bsky.social · 14/03/2025
New publication -- aka what we are doing with NIH research funding. Osteoarthritis (OA) symptoms, including pain, are often blamed on cartilage loss. OA is about more than cartilage: authors.elsevier.com/sd/article/S...
authors.elsevier.com
ScienceDirect.com | Science, health and medical journals, full text articles and books.
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Boston University Chobanian & Avedisian School of Medicine @bumedicine.bsky.social · 14/03/2025
New study by BU’s Dr. Jean Liew finds people with lower bone mineral density in the subchondral bone of the knee are more likely to experience knee pain, suggesting that the structure of bone plays a key role in osteoarthritis pain: bit.ly/4hbzOx8
bit.ly
Relationship between knee pain and depth-specific measures of proximal tibial subchondral bone density
Altered subchondral bone mineral density (BMD) may be a possible contributor to osteoarthritis (OA) pain. We evaluated the relation of compartment-spe…
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Reposted by Tuhina Neogi, MD, PhD
BU/BMC Rheumatology @bu-bmc-rheum.bsky.social · 14/03/2025
New publication from @rheumcat.bsky.social @tuhinaneogi.bsky.social @treekb.bsky.social www.sciencedirect.com/science/arti... Relationship between knee pain and depth-specific measures of proximal tibial subchondral bone density
Relationship between knee pain and depth-specific measures of proximal tibial subchondral bone density

Jean W. Liew, James D. Johnston, Kathy Bacon, Na Wang, John Lynch, Cora Lewis, James Torner, Tuhina Neogi
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Reposted by Tuhina Neogi, MD, PhD
Ewan St. John Smith @psalmotoxin.bsky.social · 10/03/2025
Cool overview of #osteoarthritis, which will be of interest to many in #neuroskyence & #PainResearch communities. Thanks to @tuhinaneogi.bsky.social, @jointsintheworld.bsky.social & others! Some figures that will doubtless appear in many talks in years to come! www.nature.com/articles/s41...
This figure shows the healthy joint (part a) and osteoarthritic joint (part b). Almost all tissue structures in osteoarthritis joint tissues show pathological changes, including articular cartilage degradation, fibrosis and inflammation of the synovium and infrapatellar fat pad, subchondral bone remodelling, meniscal damage and ligament damage.This figure outlines the hierarchical relationship between individual-level (influenced by genetic, systemic and lifestyle factors) and joint-level (specific to joint anatomy and function) risk factors that contribute to the susceptibility, progression and burden of osteoarthritis. Modifiable risk factors (blue) and non-modifiable risk factors (red) are also displayed.Knee osteoarthritis is one of the most common joint diseases, characterized by pathological changes that involve the degradation of articular cartilage, inflammation and fibrosis of the synovium and infrapatellar fat pad, and remodelling of the subchondral bone. Cartilage degradation is driven by the excessive activity of matrix metalloproteinases (MMPs) and ADAMTS enzymes, leading to the breakdown of collagen and proteoglycans, resulting in cartilage becoming thinner and cracked, compromising its cushioning function, and causing joint pain and stiffness. Meanwhile, synovial tissue shows chronic inflammation, including congestion, synovial cell hyperplasia and inflammatory cell infiltration, increasing inflammatory factors in the synovial fluid and further damaging the cartilage. The infrapatellar fat pad is also affected, with fibrosis potentially altering mechanical properties around the joint, affecting movement. The subchondral bone undergoes significant structural changes such as sclerosis and abnormal remodelling, which can lead to osteophyte formation, altering joint mechanics and increasing cartilage load. The sclerosis changes stress distribution within the joint, exacerbating cartilage damage. These pathological processes are interconnected, forming a complex network where inflammatory factors, such as IL-1β, IL-6 and TNF, further promote cartilage degradation and synovial inflammation. Mechanical stress signals activate chondrocytes and bone cells, accelerating lesion progression. Senescence-associated secretory phenotype (SASP) factors from chondrocytes or matrix-degrading enzymes secreted by osteoclasts and synovium/fat pad cells interact to exacerbate tissue damage, highlighting the importance of understanding these cellular and molecular interactions for effective osteoarthritis treatment. ARGS, aggrecanase generated aggrecan amino acids alanine, arginine, glycine, serine.a, Overview of the peripheral pain pathway in joint pain. Noxious stimuli activate the peripheral terminals of nociceptors that innervate joint tissues. Depolarization of nerve terminals initiates the firing of action potentials that invade the dorsal root ganglia, where the cell bodies reside. This requires the activation of voltage-gated sodium channels NaV1.7, NaV1.8 and NaV1.9. Signals are transmitted to the dorsal horn of the spinal cord, where nociceptors synapse with second-order neurons — either interneurons (not shown) or projection neurons that cross to the contralateral side and carry the signal up the spinal cord. From there, the signals are propagated to higher regions of the central nervous system and different areas of the brain, where they are perceived as pain. b, Peripheral terminals of nociceptors express voltage-gated sodium channels and ion channels, such as TRPV1, or mechanosensitive ion channels such as Piezo2. They also express receptors for inflammatory mediators released by degrading and inflamed joint tissues, such as nerve growth factor (NGF), CCL2 or disease-associated molecular patterns (DAMPs). c, Anatomical neuroplasticity occurs as part of osteoarthritis pathology, including neo-innervation of the synovium and sprouting of nociceptors in the subchondral bone, which may breach the tidemark.
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