New study reveals early bone changes in osteoarthritis, offering clues for earlier detection and treatment

Research at the Buck Institute uses spatial mass spectrometry to create new “molecular maps” of the knee joint

Scientists at the Buck Institute for Research on Aging and collaborators have discovered new molecular changes in knee joints affected by osteoarthritis (OA) that could help researchers detect and treat the disease earlier.

Osteoarthritis is the most common joint disease worldwide and becomes more common with age. It causes pain, stiffness, and loss of mobility for millions of older adults. Today, treatments mainly focus on managing symptoms, and many patients eventually require joint replacement surgery. One reason better treatments are difficult to develop is that scientists still do not fully understand how osteoarthritis begins and progresses at the molecular level.

In a study now online in Bone Research, scientists used an advanced imaging technology called spatial mass spectrometry imaging to create detailed molecular maps of human knee tissue. This technique allowed researchers to see exactly where specific proteins are located inside joint tissues, including cartilage and the bone underneath it.

The study found that the bone just beneath joint cartilage—called subchondral bone—shows clear molecular signs of damage in osteoarthritis. Importantly, these bone changes were sometimes detected even in areas where cartilage still appeared healthy. This suggests osteoarthritis may begin in the bone earlier than previously thought.

Researchers also identified specific structural proteins, including several types of collagens, that were increased in damaged bone tissue. These proteins help form the supportive framework of joint tissues, and changes in them may contribute to joint breakdown. Encouragingly, some of these same protein markers were also detected in joint fluid, raising the possibility of developing future tests that could help diagnose or track osteoarthritis without invasive procedures.

“This study gives us a much clearer picture of what osteoarthritis looks like at the molecular level,” said senior author Dr. Birgit Schilling professor at the Buck Institute. “By understanding how joint tissues change with aging and disease, we can begin to identify earlier warning signs and develop better ways to slow or prevent joint damage.”

The researchers note that larger studies are needed to confirm these findings and to determine whether these molecular changes appear in earlier stages of disease. The team hopes their work will help advance new diagnostic tools and therapies aimed at preserving joint health as people age.

CITATION: Tissue and extracellular matrix remodeling of the subchondral bone during osteoarthritis of knee joints as revealed by spatial mass spectrometry imaging

DOI: 10.1038/s4143-025-00495-0

 Other collaborators include Charles Schurman, Joana Bons, and Qi Liu, Buck Institute; Jonathon Woo, Cristal Yee and Tamara Alliston, Department of Orthopedic Surgery UCSF Medical Center; Nannan Tao, Bruker Daltonics, San Jose, CA; Peggi Angel, Department of Pharmacology & Immunity, Medical University of South Carolina, Charleston.

COI: Dr. Birgit Schilling serves on the advisory board of MOBILion Systems (Chadds Ford)

Acknowledgments: Funding was provided by NIH grants: NIA T32 AG000266, NIA P01 AG066591, NIAMS R21 AR084303 and NIH/OD S10 OD030212, NIH/OD S10 OD038264, NIA U01 AG060906, NIDCR R01 DE019284, DOD PRORP W81XWH1810155, NIAMS P30 AR066262, DOD PRORP OR130191, NIAMS R21 AR083065, DOD HT94252310875, NCI R21 CA240148