gms | German Medical Science

Objectives: Dysbalanced bone metabolism caused by conditions like diabetes mellitus, and degenerative bone diseases, such as osteoarthritis, present surgeons and orthopaedists with challenges, especially in implantology. In cases of limited bone regeneration, implant loosening or even implant failure may occur.

The coating of bone implants with defined components of the organic extracellular matrix (ECM) represents a novel approach to improving osseointegration. Glycosaminoglycans (GAG) as natural components of ECM play an active role in the control of cell adhesion, migration, but also proliferation and differentiation of bone cells and are thus actively involved in the bone healing process.

The effect of sulfated GAG (sGAG) on bone cells isolated from patients with osteoarthritis but otherwise normal bone metabolism was analysed regarding characteristic bone cell markers, such as calcium phosphate resorption (osteoclasts) and alkaline phosphatase activity (osteoblasts). The results were compared with GAG effects on bone cells isolated from patients who suffered from diabetic neurogenic (Charcot) osteoarthopathy.

Methods: Osteoclasts and osteoblasts from patients with diabetic neuropathy were analysed for their bone cell markers and compared with cells from patients with osteoarthritis but otherwise healthy bone. Blood monocytes were isolated from patient's blood samples and differentiated into osteoclasts while treating with sulfated hyaluronan of different sulfation degrees (sHA1, sHA3). Bone fragments extracted during reconstructive foot and ankle surgery served as source for osteoblasts. Osteoclasts, treated with sHA1 and sHA3, respectively, during culture, were analysed regarding their TRAP activity and their resorption activity. Alkaline phosphatase and expression of osteogenic genes such as osteocalcin and RUNX2 were evaluated to characterise osteoblasts.

Results and conclusion: Osteoclasts generated from diabetic patients with Charcot osteoarthropathy and impaired bone metabolism showed a significantly decreased resorption activity after treatment with sHA1 and sHA3 compared to untreated cells. In contrast, osteoclasts derived from osteoarthritis patients with otherwise normal bone metabolism showed increased resorption activity when treated with sGAG.

In osteoblasts sulfated GAG altered the expression of osteocalcin and RUNX2. The expression of RUNX2, which is an essential transcription factor determining the osteogenic lineage commitment of bone marrow stromal cells, was found to be reduced in osteoblasts of diabetic patients when treated with sHA1 or sHA3, while its expression was increased after GAG treatment in osteoblasts of patients with osteoarthritis and otherwise unaltered bone metabolism.

Reduced osteoclast activity and simultaneously increased osteogenic markers secondary to GAG treatment suggests improved bone healing, osseointegration and thus potentially enhance implant performance through the addition of an artificial ECM, especially in cases of impaired bone metabolism.