What is behind Joint Pain & Arthritis
Cartilage, synovium, subchondral bone and the tissues that load them. A finding the evidence shows: joint pain and joint structure come apart — pain 'may not correlate with inflammation or structural damage', so an intervention can help one and not the other. Evidence B — Preclinical.
The protease osteoclasts use to actually cut bone apart. Cathepsin K is the principal enzyme responsible for degrading bone collagen, and it degrades both of the collagens that matter here — type I in bone and type II in cartilage. Evidence A — Human trial evidence.
The NLRP3 inflammasome — a sensor of cellular stress that ignites sterile, damage-driven inflammation. Evidence A — Human trial evidence.
The master inflammatory switch — indispensable to defend against threat, corrosive when it never stands down. Evidence B — Preclinical.
Tissue structure and remodeling. Evidence A — Human trial evidence.
Evidence on these pathways
Cathepsin K (bone collagenase) → Joint Function. “we describe the function of cathepsin K and its effect on cartilage degradation via type II collagen cleavage.” — Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis. International Journal of Molecular Sciences; 2025; volume 26; issue 7; article number 2896. doi:10.3390/ijms26072896
NLRP3 Inflammasome → Caspase-1. “The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage.” — The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. International Journal of Molecular Sciences, 2019, 20(13), 3328. doi:10.3390/ijms20133328
NLRP3 Inflammasome → Osteoarthritis. “Mechanistically, ERK5 interacted with the PYD domain of NLRP3 and mediated NLRP3 phosphorylation at serine 198, which facilitated mature inflammasome assembly, triggered pyroptosis and subsequently exacerbated OA progression.” — Inhibition of ERK5 activity ameliorates osteoarthritis by suppressing NLRP3 inflammasome-mediated chondrocyte pyroptosis. Bone Research; 2026; volume 14; article number 95. doi:10.1038/s41413-026-00573-x
NF-κB → CD38 NADase. “Regulation of CD38 expression in HASM cells involves the transcription factor NF-κB, and glucocorticoids inhibit this expression through NF-κB-dependent and -independent mechanisms.” — Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-α and dexamethasone. Respiratory Research, 2008, vol 9, 26. doi:10.1186/1465-9921-9-26
Formulas that act on these pathways
Acts on 3 of these pathways: Joint Function, Cathepsin K (bone collagenase), NF-κB.
Acts on 3 of these pathways: Joint Function, NLRP3 Inflammasome, NF-κB.
Acts on 2 of these pathways: NLRP3 Inflammasome, NF-κB.
Acts on 2 of these pathways: NLRP3 Inflammasome, NF-κB.
Acts on 2 of these pathways: NLRP3 Inflammasome, NF-κB.
What this page does not claim
This page names the pathways involved and the published evidence on each. It does not claim that any formula treats, cures or prevents Joint Pain & Arthritis. A pathway opens here only on graded, published evidence, under a standard fixed before the evidence was gathered, and every figure above carries its grade.
These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.