Serum BMP-2, 4, 7, and AHSG in Healthy Humans

Background: BMPs are important local regulators in tissue development and repair, which were first identified based on their unique ability to induce heterotopic bone formation in soft connective tissues. Traumatic heterotopic ossification can occur in a variety of non-osteogenic mesenchymal tissues. The serum protein alpha-2HS glycoprotein (AHSG), a reverse acute phase reactant, inhibits BMPs.

Thus heterotopic ossification may develop in patients with elevated levels of circulating BMPs and/or inadequate levels of ASHG. However, there is currently no information available on the levels of circulating BMPs.

Objectives: To quantify serum levels of BMP-2, 4, 7 and AHSG in healthy individuals and determine variations based on age and sex. CRP levels were also measured as a marker of inflammation.

Materials and Methods: Serum samples from a pilot set of 16 and a larger set of 120 human subjects (60 males, 60 females, aged 20 to 72) were assayed using commercially available ELISA kits.

Results: All samples had measurable levels of BMP-2 (range 12.3 – 127.6pg/ml). BMP-4 and BMP-7 were only measurable in a fraction of the samples (range 0.0 – 250pg/ml and 0.0 – 561.4pg/ml, respectively). AHSG was present in all samples (range 176 – 1823µg/ml). BMP-2 and BMP-4 were higher in males than females (P=0.012 and 0.007, respectively), while AHSG levels declined with age (r=-0.365, P<0.001). A weak positive correlation between AHSG and BMP-7 was found (r=0.422, P<0.001).

Conclusion: We are able to detect for the first time serum levels of BMP-2, 4 and 7 in healthy humans. Our results serve as a set of standard control data displaying similarities and differences of these proteins based on age and sex and can be used as a reference for future investigations on BMP levels in disease.