Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing

Abstract

Purpose of Review: This scoping review aims to evaluate the molecular mechanisms, therapeutic potential, and safety concerns of Body Protective Compound-157 (BPC-157) in the context of musculoskeletal healing. Given the compound’s increasing availability, popularity, and its regulatory controversies, we sought to assess the breadth and quality of preclinical and clinical data supporting its use in musculoskeletal medicine.

Recent Findings: BPC-157 is a synthetic pentadecapeptide originally isolated from gastric juice and has demonstrated regenerative properties across numerous animal models. It activates several overlapping pathways, notably VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis, promoting angiogenesis, fibroblast activity, and neuromuscular stabilization. It also engages ERK1/2 signaling, facilitates endothelial and muscle repair, and exerts anti-inflammatory effects. These effects promote angiogenesis, fibroblast activity, and neuromuscular stabilization, particularly in poorly vascularized tissues such as tendons and myotendinous junctions. Despite broad preclinical support, human data are extremely limited. Only three pilot studies have examined BPC-157 in humans, including its use for intraarticular knee pain, interstitial cystitis, and intravenous safety/pharmacokinetics. No adverse effects were reported, but rigorous, large-scale trials are lacking.

Summary: BPC-157 demonstrates robust regenerative and cytoprotective effects in preclinical studies, positioning it as a potentially valuable tool in musculoskeletal medicine. Despite its growing popularity among athletes and its wide availability through non-regulated sources, there is minimal human data available. Until well-designed clinical trials are conducted, BPC-157 should be considered investigational, and its use approached with caution. This review highlights that given the robust preclinical evidence and high public interest, there is a critical need for well-designed human trials to assess the safety, efficacy, and clinical utility of BPC-157 in musculoskeletal medicine.

Keywords: Musculoskeletal medicine; Pentadecapeptide; Research gaps; Scoping review.

Fig. 1

Diagram illustrating the molecular mechanisms by which BPC-157 promotes tissue regeneration, cytoprotection, and neuromodulation. BPC-157 activates VEGF-dependent (via VEGFR2–PI3K–Akt–eNOS) and VEGF-independent (via Src–caveolin-1–eNOS) pathways to NO production, supporting angiogenesis, vasodilation, and vascular stability. It upregulates cytoprotective factors such as heme oxygenase-1 (HO-1) and heat shock proteins, preserving mitochondrial integrity and reducing oxidative stress. BPC-157 also restores glutamatergic signaling after NMDA receptor overactivation (e.g., ketamine, MK-801 exposure) and modulates adrenergic balance by counteracting beta-adrenergic overstimulation and blockade, preventing vascular occlusion-like syndromes. In endothelial cells, BPC-157 activates ERK1/2 signaling, enhancing proliferation, migration, and vascular tube formation through transcription factors like c-Fos, c-Jun, and Egr-1; ERK1/2 activation is required for its pro-healing effects both in vitro and in vivo, including in alkali-burn wound models