Osteopontin is a protein gaining attention for its connections to hair biology. While primarily recognized for its roles in bone formation and immune responses, it is now emerging as a player in the complex processes governing hair growth. Researchers are exploring how this protein influences the hair growth cycle, opening new avenues for understanding and addressing various hair-related conditions.
Understanding Osteopontin
Osteopontin (OPN) is a non-collagenous protein found in many body tissues, including bone, kidney, and skin. It promotes cell adhesion, facilitates cell migration, contributes to tissue remodeling, and plays a part in inflammatory responses and mineralization.
Within the skin, osteopontin is present in various cell types and is particularly relevant to the hair follicle. Its presence suggests a role in maintaining skin integrity and regulating cellular activities.
Osteopontin’s Influence on Hair Growth Cycle
Osteopontin impacts the cyclical nature of hair growth, which includes distinct phases: anagen (growth), catagen (regression), and telogen (resting). Anagen is the longest phase, where hair actively grows, lasting 2 to 8 years for scalp hair. Catagen is a brief transitional phase, lasting about two weeks, during which the hair follicle shrinks and detaches from the dermal papilla. The telogen phase, lasting 2 to 3 months, is a resting period before new hair begins to form and old hair sheds.
Recent research indicates that osteopontin plays a role in stimulating hair follicle stem cells, promoting their activation and hair growth. These stem cells, located in the hair follicle bulge region, regenerate new hair follicles and are dormant during the telogen phase. Osteopontin can prompt these dormant stem cells to become active, initiating a new anagen phase. This activation occurs through the osteopontin/CD44 pathway, where osteopontin binds to the CD44 receptor on hair stem cells, triggering their activity.
Osteopontin also influences dermal papilla cells, mesenchymal cells at the base of the hair follicle that regulate hair growth. While some studies suggest osteopontin can stimulate hair growth, others indicate that certain osteopontin-derived peptides can inhibit hair growth by promoting premature catagen development and decreasing fibroblast growth factor-7 (FGF-7) production in outer root sheath keratinocytes. This suggests a nuanced role for osteopontin, where its fragments or specific concentrations might have varying effects on different stages of the hair cycle.
Targeting Osteopontin for Hair Health
Current research explores manipulating osteopontin levels or activity as a therapeutic strategy for hair growth or preventing hair loss. In conditions like hairy skin moles, where excessive hair growth occurs, osteopontin levels are elevated. This has inspired investigations into how increasing osteopontin could stimulate dormant hair follicle stem cells.
One promising area involves developing compounds that act as agonists of the osteopontin/CD44 pathway. An osteopontin-based compound, AMP-203, is undergoing pre-clinical development to stimulate hair follicle stem cells and promote new hair growth.
Conversely, for unwanted hair growth, research explores osteopontin-derived peptides that inhibit hair growth. For instance, FOL-005, a modified osteopontin-derived peptide, reduces hair growth in human hair follicles by promoting premature catagen development. It achieves this by decreasing fibroblast growth factor-7 production in outer root sheath keratinocytes. These findings highlight the potential for both stimulating and inhibiting hair growth by modulating osteopontin pathways.