Researchers have identified the SHP protein as a key regulator that suppresses cartilage-degrading enzymes and slows osteoarthritis progression.
For millions of people living with osteoarthritis, treatment options have long focused on one thing: managing pain. But while medications and injections may temporarily ease aching knees and stiff fingers, they do little to stop the slow destruction of cartilage that lies at the heart of the disease.
Now, scientists in South Korea say they may have uncovered a powerful new way to protect joints before the damage becomes irreversible.
In a new study published in Nature Communications, researchers identified a protein called SHP (NR0B2) that appears to act as a natural defender of cartilage. The team found that SHP levels decline as osteoarthritis progresses, accelerating joint deterioration. Restoring the protein in animal models not only reduced cartilage damage but also improved joint function and eased pain, raising hopes for therapies that could one day slow or even halt the disease itself.
The research was led by Dr. Chul-Ho Lee and Dr. Yong-Hoon Kim at the Laboratory Animal Resource Center of the Korea Research Institute of Bioscience and Biotechnology (KRIBB), in collaboration with Prof. JinHyun Kim at Chungnam National University Hospital.
SHP protects vulnerable cartilage
To investigate SHP’s role, the researchers analyzed cartilage tissue from osteoarthritis patients as well as animal models of the disease. They discovered that SHP protein levels dropped sharply as osteoarthritis advanced, suggesting that the loss of this protective molecule may contribute directly to cartilage breakdown.
Further experiments revealed just how important the protein may be. Mice lacking SHP developed more severe pain and experienced faster cartilage degeneration than normal mice. In contrast, restoring SHP levels in affected joints significantly reduced cartilage damage and improved mobility, highlighting the protein’s potential as a therapeutic target.
A pathway slows cartilage breakdown
The mechanistic work showed that SHP helps defend cartilage by reducing the production of enzymes that destroy the tissue, especially MMP-3 and MMP-13.
These enzymes are known to break down cartilage. For the first time, the researchers showed that SHP blocks these enzymes at the signaling level by controlling the IKKβ/NF-κB pathway, helping preserve cartilage structure.
Gene delivery reduces damage
The team then tested whether SHP could be used therapeutically through gene delivery. After injecting a viral vector carrying the SHP gene into affected joints, the researchers observed lasting benefits from a single treatment.
Even in animals that already had osteoarthritis, the approach significantly reduced cartilage damage and relieved pain.
“This study is the first to demonstrate that the SHP protein plays a critical role in protecting cartilage during the development and progression of osteoarthritis,” said Dr. Chul-Ho Lee, the study’s lead investigator. “Therapeutic strategies targeting SHP may offer a new approach to slowing or preventing osteoarthritis progression.”
Reference: “Small heterodimer partner protects against osteoarthritis by inhibiting IKKβ/NF-κB-mediated matrix-degrading enzymes in chondrocytes” by Eun-Jung Kang, Jung-Ran Noh, Jae-Hoon Kim, Ji Ah Park, Jeong-Pin Ahn, Min-Chan Kim, Jung Hyeon Choi, Young-Keun Choi, In-Bok Lee, Dong-Hee Choi, Yun Jeong Seo, Yoon Seok Jung, Kyoung-Shim Kim, Jung Hwan Hwang, Yong-Bum Kim, Jong-Soo Lee, Bon Jeong Ku, Jin-Ok Jeong, Hueng-Sik Choi, Jinhyun Kim, Yong-Hoon Kim and Chul-Ho Lee, 21 February 2026, Nature Communications.
DOI: 10.1038/s41467-026-69864-5
This research was supported by the Mid-career Researcher Program of the Ministry of Science and ICT and by the Major Research Programs of the Korea Research Institute of Bioscience and Biotechnology (KRIBB).
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