Table 3.
In vitro effects of melanocortin peptides and β-ED in the osteoarticular system
| Process | Effect | Molecule | Cell type | Ref. |
|---|---|---|---|---|
| Cell survival and differentiation | VEGF induction, increased survival and maturation of osteoblasts | ACTH | BMSC (h), MG63 (h), osteoblasts (h), BHSC (h), MC3T3-E1 (m) | 196 |
| Proliferation and differentiation | Induction of proliferation and differentiation of osteoblasts | ACTH | SaOs2 (h), osteoblasts (h) | 190 |
| Gene expression | Modulation of mRNA and protein expression of MMP, IL-6, TNF, Sox9, and collagens | α-MSH | Chondrocytes (h) | 177 |
| Modulation of inflammatory cell responses | Reduction of TNF-mediated MMP-13 expression, reduced p38 phosphorylation and NF-κB activation | α-MSH | HTB-94 (h) | 183 |
| Cytokine induction | Increased IL-1β secretion, increase of MAPK 1/2 and JNK phosphorylation, decrease of p38 phosphorylation | β-ED | Chondrocytes (h) | 192 |
| Terminal differentiation | Increase of intracellular free Ca2 + | ACTH | Chondrocytes (r) | 17 |
| Proliferation and cell survival | Decrease in metabolic activity and induction of apoptosis | β-ED | Synovial cells from CIA (r) | 195 |
| Cytokine production | Reduction of LPS-induced mRNA expression of TNF, IL-1β RANTES, iNOS, MMP-2 and MMP9 | β-ED | Synovial cells from CIA (r) | 195 |
| Proliferation | Increase of [3H]thymidine incorporation | ACTH, α-, β-, γ-MSH | MG63 (h), osteoblasts (h) | 184 |
| Cytokine induction | Increased IL-1β and TNF secretion | β-ED | Chondrocytes (h) | 191 |
| Proliferation and differentiation | Increased proliferation and osteoclastogenesis | α-MSH | Osteoblasts (r), chondrocytes (d),, BMSC (m), calvaria organ culture (m) | 12 |
| Proliferation and chondrogenesis | Increased proliferation, proteoglycan matrix deposition, total collagen production, and col2a1, col8a1, and col10a1 gene expression | ACTH | BMSC (r), RCJ3.1 (r), chondrocytes (r), RCJ3.1C5.18 (r) | 182 |
| Transcription factor modulation | Decreased CREB phosphorylation | β-ED | Chondrocytes (h) | 181 |
| Cytokine production | Modulation (mostly reduction) in IL-6 and IL-8 secretion | β-ED | Synovial fibroblasts (h) | 193 |
Effects are arranged in chronological order. BMSC, Bone marrow-derived mesenchymal stem cells; BHSC, bone marrow-derived hematopoietic stem cells; d, dog; h, human; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide; m, murine; MC3T3, murine chondrocytic cell line; r, rat; RCJ3.1C5.18, rat chondrocytic cell line.