Macrophage-derived growth factor for osteoblast-like cells and chondrocytes.

Abstract

Rat resident peritoneal macrophages in primary culture were found to elaborate a mitogenic factor (or factors) for rat osteoblast-like cells and chondrocytes but not for skin fibroblasts. Growth-promoting activity appeared in the incubation medium within the first 20 hr of macrophage culture and was released in amounts that paralleled the number of macrophages per culture. After their proliferative response, as judged by increases in DNA synthesis and cell number, the osteoblast-like cells became enriched in alkaline phosphatase, an index of osteoblast specialization. The macrophage-derived activity was nondialyzable and heat-stable, and it was eliminated by exposure to trypsin. Inhibition of prostaglandin cyclooxygenase failed to modify its generation. Partial purification (Amicon filter concentration, gel filtration) disclosed principal peaks of activity corresponding to Mr of 43,000 and 10,000. The crude conditioned medium and the Mr 43,000-peak, but not the low-molecular-weight peak, exhibited interleukin 1 activity, as judged by the ability to stimulate the proliferation of mouse thymic lymphocytes. The macrophagederived growth factor described herein may participate in bone remodeling and repair and in primary bone and cartilage growth.The mammalian skeleton is a dynamic tissue, undergoing virtually continuous turnover after its initial development (1). Skeletal turnover stems from a complex remodeling process of microscopic dimensions in which osteoclasts resorb bone mineral and organic matrix and osteoblasts proceed to repair the resorption cavity (2, 3). Resorptive and formative events at each remodeling locus are congruent in space, sequentially coupled in time, and balanced in quantity, so that the mass of bone does not change, at least not in the short term. This spatial, temporal, and quantitative coordination points to the participation of local signals in the control of remodeling, and it has prompted a search for locally elaborated regulatory factors. Cells of the monocyte macrophage series may well generate such factors. Not only are they thought to be the precursors of mature osteoclasts (4-12), they are known to release agents that promote bone resorption both directly and indirectly (13). Furthermore, macrophage-like cells occupy resorption cavities during the time interval between resorption and formation, so that they are appropriately positioned to influence formative events (14,15). We have examined the possibility that macrophages elaborate a factor (or factors) that promote(s) the proliferation of osteoblasts, thereby acting to couple formation and resorption. We describe herein a heat-stable peptide activity in macrophage-conditioned medium (MCM), which promotes the growth of osteoblasts and chondroblasts in vitro. Abbreviations: CDM, chemically defined medium; PDS, plateletpoor plasma-derived serum; IL-1, interleukin 1 (lymphocyte-activating factor); MDGF, macrophage-derived growth factor; MCM, macrophage-conditioned medium. *To whom reprint requests should be addressed. MATER...

Interleukin 1α acts as an autocrine growth factor for RPMI1788, an Epstein‐Barr virus‐transformed human B cell line

“…In this study we extended these observations, demonstrating that IL la is constitutively secreted and is involved in the autocrine circuit of RPMI 1788. IL 1 exhibits direct growth-enhancing activity on many cell types: fibroblasts [23], mesanglial cells [24], osteoblasts and chondrocytes [25], as well as anti-p-stimulated normal B cells [26].…”

Growth factors and the regulation of bone remodeling.

“…In addition to IL-1 and TNFa, the macrophage secretes other polypeptides with effects on bone remodeling in vitro, such as macrophage-derived growth factor and a PDGF-like molecule (35).…”

Growth factors as autocrine and paracrine modulators of male gonadal functions

“…The mature, biologically active, IL-la and IL-Iß, have similar Mr values but pi values of 5 and 7, respectively. The two polypeptides, now available in recombinant forms, share only a low level of homology (Dinarello, 1988 (Postlethwaite et al, 1984), glial cells (Guilian & Larchman, 1985), osteoblasts (Rifas et al, 1984) and chondrocytes (Madsen & Soder, 1986 (Bergh, 1985) and be responsive to FSH. Studies on one or all of these proposed functions could identify new autocrine and paracrine pathways for regulating spermatogenesis.…”