Researchers uncover the protective role of LOXL2 protein in preventing cartilage damage

Osteoarthritis in the jaw joint, or TMJ osteoarthritis, affects millions worldwide, yet effective treatments are limited. Researchers from Boston University now report that a naturally occurring enzyme called LOXL2 could help protect joint cartilages from inflammation and cell death, which are the major drivers of arthritis. Findings suggest that boosting this enzyme could be a promising strategy in treating jaw arthritis—inspiring future therapies for preserving joint function.

Our joints rely on smooth, resilient cartilage and disc, which act as natural shock absorbers to enable painless movement. However, when these cartilages wear down due to conditions like arthritis, their cushioning effect decreases and leads to stiffness, inflammation, and severe joint pain. One such condition is temporomandibular joint osteoarthritis (TMJ-OA), a degenerative condition that affects the cartilage of the temporomandibular joint (TMJ)—a hinge-like joint connecting your lower jaw to the skull.

Surprisingly, despite the prevalence of TMJ-OA, there are currently no FDA-approved drugs specifically designed to protect or regenerate cartilage in this joint. Addressing this issue, a team of researchers from Boston University has made a compelling discovery for TMJ-OA, reporting how an enzyme called lysyl oxidase-like 2 (LOXL2) plays a critical role in maintaining cartilage health and preventing arthritis-like damage.

The study was led by Assistant Professor Manish V. Bais along with fellow researchers from Boston University and the University of Pittsburgh, USA. Their findings were made available online in the International Journal of Oral Science on February 4, 2026. Using genetically modified mice lacking the Loxl2 gene and cartilage samples from goats, which closely resemble human jaws, the researchers carefully analyzed the role of LOXL2.

“Cartilage deterioration is a hallmark of osteoarthritis,” notes Prof. Bais. Normally, the cartilage tissue is maintained by a group of specialized cells called chondrocytes. But during osteoarthritis, this balance is disrupted, and inflammatory molecules, like interleukin-1 beta (IL-1β), start activating destructive pathways inside the joint.

“We observed that the loss of loxl2 activates inflammatory genes and weakens the cartilage by reducing its essential structural components such as aggrecanproteoglycans and promote inflammatory factors,” explains Prof. Bais

To understand why this happens, the team focused on the NF-κB (nuclear factor kappa B) molecular pathway, which is often described as a “master switch” for inflammation. When activated, this pathway instructs cells to produce factors that worsen tissue damage. The researchers noted that LOXL2 helps suppress this pathway, thereby reducing inflammation and preventing chondrocytes from undergoing cell death. Furthermore, it also protected the cell’s mitochondria from inflammatory attacks while preserving its activity and energy production. This allowed the cartilage cells to remain viable even under inflammatory conditions.

Interestingly, when cartilage samples were treated with additional LOXL2, the enzyme reversed many harmful effects caused by inflammation. For instance, it significantly reduced the expression of molecules linked to pain and cartilage destruction (such as MMP13, ADAMTS5, and PTGS2) and restored the protective tissue components of the cartilage. Confirming these effects in goat tissue further strengthened their clinical relevance, as goat jaw joints are structurally quite similar to human jaw joints.

“Our findings identify LOXL2 as a promising therapeutic target for TMJ disorders. By safeguarding cartilage and preventing cell death, this enzyme may have the potential to slow down or even stop the progression of arthritis in the jaw,” emphasizes Prof. Bais.

While the authors do acknowledge the need for additional clinical studies to confirm these effects in humans, this study marks a significant step towards developing targeted therapies for TMJ disorders that could help patients preserve joint function, reduce pain, and improve their overall quality of life.

Reference
Title of original paper: LOXL2 deletion triggers TMJ osteoarthritis, while overexpression protects it from NF-κB-induced chondrocyte apoptosis
Journal: International Journal of Oral Science
DOI: https://doi.org/10.1038/s41368-025-00409-0

About Boston University, Boston, Massachusetts:
Founded in 1839, Boston University is a leading private research institution in Boston, Massachusetts. With more than 37,000 students from over 140 countries, the University is dedicated to advancing knowledge across diverse fields, including the sciences, medicine, engineering, arts, and humanities. Guided by a vision to foster innovation and interdisciplinary collaboration, Boston University prepares students to become global leaders in an increasingly complex and interconnected world while driving discoveries that address society’s most pressing challenges.
Website: https://www.bu.edu/

About Prof. Manish V. Bais from Boston University, Boston
Dr. Manish V. Bais is an Associate Professor of Translational Dental Medicine at Boston University’s Henry M. Goldman School of Dental Medicine, Boston. Here he leads the Bais lab, which focuses on translational research at the intersection of cancer biology, regenerative medicine, and immunology. He earned his PhD in Biotechnology and Veterinary Medicine from the Indian Veterinary Research Institute (IVRI), India, in 2004. He has authored more than 40 peer-reviewed research articles, with his work primarily focusing on oral cancer biology, temporomandibular joint disorders, and regenerative medicine.
Bais research group website: https://sites.bu.edu/baislab/

Funding information
This study was supported by an NIH grant R01 DE031413 (M.V.B.).